Category Archives: Genetic Engineering

UC San Diego scientists have modified the genome of fruit flies using CRISPR-based technologies to create eight reproductively isolated species. In the future, this technique can be adapted to other organisms including plants, insects and vertebrates to provide new biocontrol opportunities. Credit: Akbari lab, UC San Diego

Researchers create novel CRISPR-based fly species as a new method of controlling gene drive spread.

CRISPR-based technologies offer enormous potential to benefit human health and safety, from disease eradication to fortified food supplies. As one example, CRISPR-based gene drives, which are engineered to spread specific traits through targeted populations, are being developed to stop the transmission of devastating diseases such as malaria and dengue fever.

But many scientists and ethicists have raised concerns over the unchecked spread of gene drives. Once deployed in the wild, how can scientists prevent gene drives from uncontrollably spreading across populations like wildfire?

Now, scientists at the University of California San Diego and their colleagues have developed a gene drive with a built-in genetic barrier that is designed to keep the drive under control. Led by molecular geneticist Omar Akbaris lab, the researchers engineered synthetic fly species that, upon release in sufficient numbers, act as gene drives that can spread locally and be reversed if desired.

The scientists describe their SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species) development as a proof-of-concept innovation that could be portable to other species such as insect disease vectors. Spreading gene drives that limit pests that feast on valuable food crops is another example of a potential SPECIES application.

Gene drives can potentially spread beyond intended borders and be hard to control. SPECIES offers a way to control populations in a very safe and reversible manner, said Akbari, a UC San Diego Division of Biological Sciences associate professor and senior author of the paper, which is published in the journalNature Communications.

The idea behind the creation of SPECIES is reflective of the formation of new species in nature. As members of a single species separate over time, due to, for example, a new land formation, earthquake separation or other geological event, a new species eventually can evolve from the physical disconnection. If the new species eventually returns to mate with the original species, they could produce unviable offspring due to biological changes following the separation through a natural phenomenon known as reproductive isolation.

Working in the fly species Drosophila melanogaster, UC San Diego researchers and their colleagues at the California Institute of Technology, UC Berkeley and the Innovative Genomics Institute used CRISPR genetic-editing technologies to develop flies encoding SPECIES systems that are reproductively incompatible with wild versions of D. melanogaster.

Even though speciation happens consistently in nature, creating a new artificial species is actually a pretty big bioengineering challenge, said Anna Buchman, the lead author of the paper. The beauty of the SPECIES approach is that it simplifies the process, giving us a defined set of tools we need in any organism to elegantly bring about speciation.

Conceptually, when SPECIES are deployed in the wild in sufficient numbers, they can controllably drive through a population and replace all of their wild counterparts as they spread. Using malaria as an example, SPECIES mosquitoes could be developed with a genetic element that makes them incapable of transmitting malaria.

You can spread an anti-malaria SPECIES into a target population in a confinable and controllable way, said Akbari. Since SPECIES are incompatible with wild-type mosquitoes, their populations can be controlled and reversed by limiting their threshold population below 50 percent. This gives you the ability to confine and reverse its spread if desired.

As the SPECIES barrier completes its role in temporarily replacing wildtype populations, their numbers can be reduced with the reintroduction of wild type populations.

This essentially allows us to harness all of the power of gene driveslike disease elimination or crop protectionwithout the high risk of uncontrollable spread, said Akbari.

Reference: Engineered reproductively isolated species drive reversible population replacement by Anna Buchman, Isaiah Shriner, Ting Yang, Junru Liu, Igor Antoshechkin, John M. Marshall, Michael W. Perry and Omar S. Akbari, 2 June 2021, Nature Communications.DOI: 10.1038/s41467-021-23531-z

Coauthors of the paper include Anna Buchman, Isaiah Shriner (former UC San Diego undergraduate student), Ting Yang, Junru Liu (current Biological Sciences PhD student), Igor Antoshechkin, John Marshall, Michael Perry and Omar Akbari.

Funding: UC San Diego, DARPA Safe Genes Program

Continue reading here:
Researchers Engineered a New Synthetic Fly Species Here's Why - SciTechDaily

Scientists have developed a synthetic strain of Escherichia coli that can construct artificial polymers from building blocks that are not found in nature, by following instructions that the researchers encoded in their genes. The scientists, led by a team at the Medical Research Council (MRC) Laboratory of Molecular Biology, engineered the genetic code of the E. coli strain to include several nonstandard amino acids, and found that this synthetic genome made the bacteria entirely resistant to infection by viruses.

The work is some of the first to design proteins that incorporate multiple non-canonical amino acids. The team suggests that their work, and achievement could lead to the development of new polymers such as proteins and plastics, and drugs including antibiotics, as well as making it easier to manufacture drugs reliably using bacteria.

The newly reported achievement builds on previous ground-breaking work by researchers who, in 2019, developed a new techniques to create the biggest ever synthetic genomeconstructing the entire E. coli genome from scratch. Commenting on the latest developments, study lead, Jason Chin, PhD, from the MRC Laboratory of Molecular Biology, said, These bacteria may be turned into renewable and programmable factories that produce a wide range of new molecules with novel properties, which could have benefits for biotechnology and medicine, including making new drugs, such as new antibiotics.

The investigators report on their latest development in Science, in a paper titled, Sense codon reassignment enables viral resistance and encoded polymer synthesis.

The genetic code instructs a cell how to make proteins, which are constructed by joining together strings of natural (canonical) amino acid building blocks. The genetic code in DNA is made up of four bases, represented by the letters: A, T, C and G. When a peptide or protein is being constructed, the four letters in DNA are read in groups of three letters, or codonsfor example TCG. Each codon tells the cell to add a specific amino acid to the peptide chain, which it does via molecules called transfer RNA (tRNA). Each codon is recognized by a specific tRNA, which then adds the corresponding amino acid. For example, the tRNA that recognizes the codon TCG, brings the amino acid serine.

With four letters in groups of three, there are 64 possible combinations of letters, but there are only 20 different canonical amino acids that cells commonly use. So, several different codons can be synonymousthey all code for the same amino acid for example, TCG, TCA, AGC and AGT all code for serine. There are also codons which tell a cell when to stop making a protein, such as TAG and TAA.

Its thought that removing certain codons and the transfer RNAs that read them from the genome and replacing them with noncanonical amino acids (ncAAs) may enable the creation of synthetic cells with properties not found in natural biology, including powerful viral resistances and enhanced biosynthesis of novel proteins. However, these hypotheses have not been experimentally tested, the authors wrote. And to date, the approach has been largely restricted to the incorporation of a single ncAA into a polypeptide chain. As the team noted, limitations preclude the synthesis of noncanonical heteropolymer sequences composed entirely of noncanonical monomers.

In 2019, the team at the MRC Laboratory of Molecular Biology created the first entire genome synthesized from scratch for the commonly studied bacteria, E. coli. They also took the opportunity to simplify its genome. In this engineered strain the scientists replaced some of the codons with their synonyms. So, they removed every instance of TCG and TCA and replaced them with the synonyms AGC and AGT. They also removed every instance of the stop codon TAG and replaced it with its synonym TAA. This meant that the modified bacteria no longer had the codons TCG, TCA and TAG in their genome, but they could still make normal proteins and live and grow.

The MRC scientists goal was to utilize their new technology to create the first cell that can assemble polymers entirely from building blocks that are not found in nature. For the newly reported studies, the scientists further modified the bacteria to remove the tRNA molecules that recognize the codons TCG and TCA. This means that, even if there are TCG or TCA codons in the genetic code, the cell no longer has the molecule that can read those codons.

This is fatal for any virus that tries to infect the cell, because viruses replicate by injecting their genome into a cell and hijacking the cells machinery. Virus genomes still contain lots of the TCG, TCA and TAG codons, but the modified bacteria are missing the tRNAs to read these codons. So when the machinery in the modified bacteria tries to read the virus genome, it fails every time it reaches a TCG, TCA or TAG codon.

When the researchers infected their bacteria with a cocktail of viruses, they confirmed that while unmodified, control bacteria were killed by these pathogens, the modified bacteria were resistant to infection and survived.

Many drugsfor example, protein drugs, such as insulin, and polysaccharide and protein subunit vaccinesare manufactured by growing bacteria that contain instructions to produce the drug. So making bacteria that are resistant to viruses could make manufacturing certain types of drugs more reliable and cheaper. Chin explained, If a virus gets into the vats of bacteria used to manufacture certain drugs then it can destroy the whole batch. Our modified bacterial cells could overcome this problem by being completely resistant to viruses. Because viruses use the full genetic code, the modified bacteria wont be able to read the viral genes. The team further wrote, We have synthetically uncoupled our strain from the ability to read the canonical code, and this advance provides a potential basis for bioproduction without the catastrophic risks associated with viral contamination and lysis.

By creating bacteria with synthetic genomes that do not use certain codons, the researchers also effectively freed up those codons to be used for other purposes, such as coding for synthetic building blocks (monomers). We reassigned these codons to enable the efficient synthesis of proteins containing three distinct noncanonical amino acids, the authors explained. For the studies detailed in Science, the team engineered the bacteria to produce tRNAs coupled with artificial monomers, which recognized the newly available codons (TCG and TAG).

They inserted genetic sequences with strings of TCG and TAG codons into the bacterias DNA. These were read by the altered tRNAs, which assembled chains of synthetic monomers in the sequence defined by the sequence of codons in the DNA. The cells were programmed to string together monomers in different orders by changing the order of TCG and TAG codons in the genetic sequence. Polymers composed of different monomers were also made by changing which monomers were coupled to the tRNAs. We incorporated three distinct ncAAs into ubiquitin, in response to TCG, TCA, and TAG, the team explained. We demonstrated the generality of our approach by synthesizing seven distinct versions of ubiquitin, each of which incorporated three distinct ncAAs.

Using their approach the scientists were able to create polymers made of up to eight monomers strung together. They joined the ends of these polymers together to make macrocyclesa type of molecule that forms the basis of some drugs, such as certain antibiotics and cancer drugs.

Chin said, This system allows us to write a gene that encodes the instructions to make polymers out of monomers that dont occur in nature. Wed like to use these bacteria to discover and build long synthetic polymers that fold up into structures and may form new classes of materials and medicines. We will also investigate applications of this technology to develop novel polymers, such as biodegradable plastics, which could contribute to a circular bioeconomy.

The synthetic monomers were linked together by the same chemical bonds that join together amino acids in proteins, but the researchers are in addition investigating how to expand the range of linkages that can be used in the new polymers. In their paper, they concluded, Future work will expand the principles we have exemplified herein to further compress and reassign the genetic code. We anticipate that, in combination with ongoing advances in engineering the translational machinery of cells, this work will enable the programmable and encoded cellular synthesis of an expanded set of noncanonical heteropolymers with emergent, and potentially useful, properties.

Commenting in an accompanying Perspective in the same issue of Science, D. Jewel, and A. Chatterjee, from Boston College in Chestnut Hill, acknowledged, The ability to generate designer proteins using multiple non-natural building blocks will unlock countless applications, from the development of new classes of biotherapeutics to biomaterials with innovative properties.

Megan Dowie, PhD, head of molecular and cellular medicine at the MRC, which funded the study, said, Dr. Chins pioneering work into genetic code expansion is a really exciting example of the value of our long-term commitment to discovery science. Research like this, in synthetic and engineering biology, clearly has huge potential for major impact in biopharma and other industrial settings.

Read more here:
Synthetic E. Coli Reprogrammed to Make Polymers from Artificial Monomers, and Resist Viral Infections - Genetic Engineering & Biotechnology News

The UK government recently announced an 800 million, taxpayer-funded Advanced Research and Invention Agency (Aria). The brainchild of the British prime ministers former chief adviser,Dominic Cummingsand modelled on the USDefense Advanced Research Projects Agency, Darpa, the organisation will focus partly on genomic research.

Genome technology is becoming an increasingly important part of military research. So given that the UK boasts some of the best genomic research centres in the world, how will its new agency affect the wider genome technology warfare race?

In 2019, Darpa announced that it wishes to explore genetically editing soldiers. It has also invested over US$65 million (45 million) to improve the safety and accuracy of genome-editing technologies. These include the famousNobel prize-winning Crispr-Cas molecular scissor a tool that can edit DNA by cutting and pasting sections of it.

But the ease of accessibility and low cost of Crispr-based technologies has caused concern around potential military genetic modification andweaponisation of viruses or bacteria. These include smallpox or tuberculosis, and could be extremely destructive.

The US is not alone in its military pursuit of genome technology. Russia and China have either stated or been accused of using genomic technology to enhance military capabilities.

Universal SoldierandCaptain Americaare just a few Hollywood movies that have explored the concept of the super soldier. Despite its sci-fi nature, several countries are looking to explore the potential of such prospects. Darpa intends to explore genetically editing soldiers toturn them into antibody factories, making them resistant to chemical or biological attacks.

In December 2020, the then US director of national intelligence,John Ratcliffe, said there was evidence that the Chinese militarywas conducting human experimentationin an attempt to biologically boost soldiers. This followed a report by theJamestown policy thinktankthat highlighted reports suggesting that Crisprwould form a keystone technologyin China to boost troops combat effectiveness. No further details were given, however.

Not all countries are prepared to use gene editing or even genomic technology to enhance soldiers, however. The French military ethics committee has recentlyapprovedresearch on soldier augmentation, such implants that could improve cerebral capacity. However, the committee warned that certain red lines could not be crossed, including genome editing or eugenics. In the morecandid words of the French minister of the armed forces,Florence Parly, this amounted to A yes to Ironman, but a no to Spiderman (Ironman gets his superpowers from a suit whereas Spiderman is bitten by a radioactive spider).

In Russia, the military is looking toimplement genetic passportsfor its personnel, allowing it to assess genetic predispositions and biomarkers, for example, for stress tolerance. This could help place soldiers in suitable military lines, such as navy, air force and so forth. The genetic project also aims to understand how soldiers respond to stressful situations both physically and mentally.

There are signs that the UK will be bolder and less accountable in its genetic defence research than many other countries. For example, Aria wont besubject to freedom of information requests, in contrasts with Darpa.

The UK has also been at the forefront in enabling controversial, pioneering non-military genome technology, such asthree-parent babies. And there has been no shortage of government reports that have stressed the importance of genome technology in the domain of defence and security.

In 2015,a UK national defence reviewhighlighted the influence that advances in genetic engineering can have for security and prosperity. In the recent 2021Security, Defence, Development and Foreign Policy reviewthe UK government once again stressed its significance for defence and national security.

The proposed lack of accountability of Aria, combined with the governments general mission for genome technology to be expanded into security and defence applications, will create a hotpot of debate and discussion. In recent years, British scientists have received Darpa fundingfor controversial genomic research, such as genetic extinction of invasive species such as mosquitoes or rodents. Despite its promise, this could have disastrous potential to damage food security and threaten the wider ecosystems of nations.

Genome technology deployment needs to be managed in a universally, ethically and scientifically robust manner. If it isnt, the potential for a new arms race for advances in this research will only lead to more radical and potentially dangerous solutions. There are many unanswered questions about how Aria will help genome research within the military sphere. The pathway the UK chooses will have lasting consequences on how we perceive genome tech in the public space.

Yusef Paolo Rabiah is a PhD Candidate at STEaPP UCL. Yusefs PhD is focused on developing public policy frameworks for the introduction of germline genome editing technologies into the UK. Find Yusef on Twitter @PaoloYusef

A version of this article was originally posted at the Conversation and has been reposted here with permission. The Conversation can be found on Twitter @ConversationUS

See the rest here:
Genomic Cold War? More nations joining the US in using biotechnology to enhance military capabilities - Genetic Literacy Project

Its a fivehour drive into the western part of Uganda to Kachwekano Zonal Agricultural Research and Development Institute (KaZARDI), where GM Irish potatoes are being bred. Visitors are welcomed by healthy looking plants, the centerpiece of the countrys ongoingpotato field trial.

The group of farmers engaged in potato farming and seed production came for a tour at the institute. KaZARDI director Alex Barekye explained to the farmers that the plants are still being researched and are likely to be released next year, but only if the government gives it a green light.

Some of the visiting farmers interrupted him, at times demanding more immediate availability of the genetically-engineered potato seed.Charles Byarugaba, a commercial potato farmer and leader of potato seed multiplication famers in Kabale, Uganda, challenged the scientists.

We want the GMO potato seed right away, he said. You can go ahead to follow those legal procedures but it must not affect us farmers because we are in need of varieties resistant to potato blight. His fellow farmers said that ifthey are not given the resistant seeds, there will be no option but to acquire them illegally.

Unfortunately, the politics of farming in Uganda, particularly when it comes to advanced biotechnology, has all but scuttled the implementation of cutting edge technologies. The countrys farmers face daunting challenges.

Our crops are facing extinction and there are no known ways of effectively dealing with the new pests and diseases other than the use of biotechnology, Dr Wilberforce Tushemeirwe, a prominent scientist, has said. Food crops such as cassava, bananas and sweet potatoes face extinction due to incurable crop diseases. Maize is under attack by the fall army worm. Cotton which is a cash crop has proven difficult to grow in Uganda because of the cotton bollworm pest infestation, which GM technology contains in many other countries.

The Genetic Engineering Regulatory law, formerly referred to as the National Biotechnology and Biosafety billhas twice come close to being signed into law. It would allow for regulated production and use of genetically modified crops in the country,and would pave the way to biotech solutions in use in dozens of other countries, including in other African countries.

However, anti GM groups have been working to ensure the GERA law is not passed. Speaker of Parliament Rebbeca Kadaga supported the law and has on two occasions tried to form a quorum of members of Parliament but to date no action has been taken.

The latest crop under siege is theIrish potato, a food security crop and is grown in the highland areas of southwestern Uganda in Kabale and Kisoro.For communities in this part of the country, it is considered staple food and a primarysource of income.

The country relies on supplies of potato from farmers in the southwest,who contribute 60% of supply, and those in the Eastern highlands of Uganda, who contribute the other 40%.As a result of increased demand from urban areas, production has intensified andis spreading into other areas of Uganda.

Read this article:
Banned in Uganda: While the Irish potato faces disease and climate change, politics stymie farmers eager to adopt still unapproved GM seeds - Genetic...

Scientists investigate the evolution of Mimivirus, one of the worlds largest viruses, through how they replicate DNA. Credit: Indian Institute of Technology Bombay

Researchers from the Indian Institute of Technology Bombay shed light on the origins of Mimivirus and other giant viruses, helping us better understand a group of unique biological forms that shaped life on Earth. In their latest study published in Molecular Biology and Evolution, the researchers show that giant viruses may have come from a complex single-cell ancestor, keeping DNA replication machinery but shedding genes that code for other vital processes like metabolism.

2003 was a big year for virologists. The first giant virus was discovered in this year, which shook the virology scene, revising what was thought to be an established understanding of this elusive group and expanding the virus world from simple, small agents to forms that are as complex as some bacteria. Because of their link to disease and the difficulties in defining themthey are biological entities but do not fit comfortably in the existing tree of life viruses incite the curiosity of many people.

Scientists have long been interested in how viruses evolved, especially when it comes to giant viruses that can produce new viruses with very little help from the hostin contrast to most small viruses, which utilize the hosts machinery to replicate.

Even though giant viruses are not what most people would think of when it comes to viruses, they are actually very common in oceans and other water bodies. They infect single-celled aquatic organisms and have major effects on the latters population. In fact, Dr. Kiran Kondabagil, molecular virologist at the Indian Institute of Technology (IIT) Bombay, suggests, Because these single-celled organisms greatly influence the carbon turnover in the ocean, the viruses have an important role in our worlds ecology. So, it is just as important to study them and their evolution, as it is to study the disease-causing viruses.

Scientists investigate the evolution of Mimivirus, one of the worlds largest viruses, through how they replicate DNA. Researchers from the Indian Institute of Technology Bombay shed light on the origins of Mimivirus and other giant viruses, helping us better understand a group of unique biological forms that shaped life on earth. Credit: Indian Institute of Technology Bombay

In a recent study, the findings of which have been published in Molecular Biology and Evolution, Dr. Kondabagil and co-researcher Dr. Supriya Patil performed a series of analyses on major genes and proteins involved in the DNA replication machinery of Mimivirus, the first group of giant viruses to be identified. They aimed to determine which of two major suggestions regarding Mimivirus evolutionthe reduction and the virus-first hypotheses were more supported by their results. The reduction hypothesis suggests that the giant viruses emerged from unicellular organisms and shed genes over time; the virus-first hypothesis suggests that they were around before single-celled organisms and gained genes, instead.

Dr. Kondabagil and Dr. Patil created phylogenetic trees with replication proteins and found that those from Mimivirus were more closely related to eukaryotes than to bacteria or small viruses. Additionally, they used a technique called multidimensional scaling to determine how similar the Mimiviral proteins are. A greater similarity would indicate that the proteins coevolved, which means that they are linked together in a larger protein complex with coordinated function. And indeed, their findings showed greater similarity. Finally, the researchers showed that genes related to DNA replication are similar to and fall under purifying selection, which is natural selection that removes harmful gene variants, constraining the genes and preventing their sequences from varying. Such a phenomenon typically occurs when the genes are involved in essential functions (like DNA replication) in an organism.

Taken together, these results imply that Mimiviral DNA replication machinery is ancient and evolved over a long period of time. This narrows us down to the reduction hypothesis, which suggests that the DNA replication machinery already existed in a unicellular ancestor, and the giant viruses were formed after getting rid of other structures in the ancestor, leaving only replication-related parts of the genome.

Our findings are very exciting because they inform how life on earth has evolved, Dr. Kondabagil says. Because these giant viruses probably predate the diversification of the unicellular ancestor into bacteria, archaea, and eukaryotes, they should have had major influence on the subsequent evolutionary trajectory of eukaryotes, which are their hosts.

In terms of applications beyond this contribution to basic scientific knowledge, Dr. Kondabagil feels that their work could lay the groundwork for translational research into technology like genetic engineering and nanotechnology. He says, An increased understanding of the mechanisms by which viruses copy themselves and self-assemble means we could potentially modify these viruses to replicate genes we want or create nanobots based on how the viruses function. The possibilities are far-reaching!

Reference: Coevolutionary and Phylogenetic Analysis of Mimiviral Replication Machinery Suggest the Cellular Origin of Mimiviruses by Supriya Patil and Kiran Kondabagil, 11 February 2021, Molecular Biology and Evolution.DOI: 10.1093/molbev/msab003

Read the rest here:
Scientists Use DNA To Trace the Origins of Giant Viruses - SciTechDaily

How will the worlds most powerful democracies deal with the ethical and legal dilemmas posed by the development of so-called killer robots, or lethal autonomous weapons systems (LAWS)? On the one hand, LAWS promise unparalleled operational advantages, like acting as a force multiplier, expanding the battlefield, and removing humans from dull, dirty, or dangerous missions. Authoritarian powers like China and Russia appear to be dedicating tremendous resources into pursuing these capabilities. On the other hand, giving autonomous weapons the authority to determine who lives or dies is an ethical, practical, and legal nightmare.A couple of states have well-documented policies, most notably the United States and the United Kingdom.

This article focuses on France, which has begun the difficult work of thinking through the ethical problems associated with lethal autonomous weapons systems. Im a member of Frances Defense Ethics Committee, which reports directly to the countrys defense minister. Last year, the committee submitted an opinion on the enhanced soldier, which drew a red line between acceptable, non-invasive practices, and unacceptable ones such as genetic engineering.

In April, the French defense ministry published another Defense Ethics Committee opinion on the integration of autonomy into lethal weapon systems. We argue that LAWS should be understood as fully autonomous weapons, which are ethically unacceptable for a number of reasons, but that partially autonomous lethal weapon systems (PALWS), which present both potential benefits and risks, could be ethically acceptable under certain conditions.

Why does it matter? Not only because, to the knowledge of this author, no other major military power has such an ethics committee playing such a role within their Ministry of Defense, and that itself tells something about the French ethos. The Defense Ethics Committees opinion on autonomous weapons is likely to be scrutinized for a number of other reasons: it was France that, in 2013, initiated the multilateral debate on autonomous weapons; it has been an active participant in the debate since then (see for example the 2017 French-German proposal); and also because France will chair the next Convention on Certain Conventional Weapons Review Conference in December 2021.

LAWS Versus PALWS

The committees first and arguably most important initial task was to define key terms. It decided to define LAWS as:

A lethal weapon system programmed to be capable of changing its own rules of operation particularly as regards target engagement, beyond a determined framework of use, and capable of computing decisions to perform actions without any assessment of the situation by human military command.

The most important aspect of this definition is its narrowness: in line with Frances position at U.N. meetings, LAWS are considered as fully autonomous systems. Defining LAWS has always been a challenge, because if understood as fully autonomous we are talking about weapons that do not yet exist. As a result, there is no shared experience or understanding with these weapons. In the history of arms control, that makes them quite unique. In multilateral fora (e.g., the United Nations), some states have used the challenge of defining LAWS as an excuse to obstruct or redirect debate. By limiting LAWS to fully autonomous weapons, France defends a restrictive approach avoiding those weapons being confused with remotely operated or supervised weapons systems, which always involve a human operator.

The committee then introduced the category of partially autonomous lethal weapon systems (PALWS). It decided to define it as:

[I]ntegrating automation and software: [1] to which, after assessing the situation and under their responsibility, the military command can assign the computation and execution of tasks related to critical functions such as identification, classification, interception and engagement within time and space limits and under conditions; [2] which include technical safeguards or intrinsic characteristics to prevent failures misuse and relinquishment by the command of two vital duties, namely situation assessment and reporting.

PALWS are an in-between category, distinct from two others. On the one hand, PALWS are not LAWS because they cannot change their own rules of operation, they cannot take lethal initiatives. On the other, PALWS are not automated weapon systems either. The difference between autonomy and automation is foundational. Once deployed, both autonomous and automated weapons can function without human involvement. However, while automation refers to the performance of a limited number of repetitive and pre-determined tasks (the system always reacts the same way to the same stimulus), autonomy involves an ability to learn and adjust in a changing environment. For example, mines and some air defense systems are automated in that they act in a reactive and repetitive way, by detonating or firing, when their sensors detect an object. They do not learn or adapt, and they do not need to because they do not have to face unexpected situations. Their environment does not change. PALWS are not LAWS in that they are not fully autonomous. However, because they are still (partially) autonomous, they are not automated weapons either. Several existing weapons could be categorized as PALWS, among which loitering munitions such as the Israeli IAI Harop, the Turkish STM Kargu-2, and a non-identified Chinese model used in swarms; the American Collaborative Small Diameter Bombs (CSDB), or the drone warship Sea Hunter.

Now, two objections could be raised at this point. First, that such a distinction between LAWS and PALWS is certainly not new in the international debate, nor in national doctrines. Indeed, as early as in 2012, when the United States was the first country to establish guidelines for the development and use of autonomy in weapon systems, they had already distinguished between an autonomous weapon system and a semi-autonomous one. If the PALWS category is a terminological innovation in French especially in a ministerial document partially and semi autonomous weapon systems, while being defined differently, do refer to the same challenge of describing what lies under the threshold of full autonomy.

Second, by adopting a narrow definition of LAWS limited to fully autonomous weapons, isnt France defining them as something nobody ever wanted? Under the appearance of rejecting LAWS, a category of systems that havent really been under consideration, isnt France actually legitimizing the more realistic category of PALWS? This is a legitimate concern. However, as a member of the committee that drafted the opinion, the intention was not to legitimize whatever category of autonomous weapons it may be. Instead, the goal was to add some needed intellectual rigor. The problem with the LAWS terminology is that autonomous is presumed to be dichotomic: a system is, or is not, autonomous. And if it is autonomous, it is presumed to be fully autonomous which, for good reasons, no one really wants. Therefore, it is more useful to adopt an alternative terminology based on the idea that the integration of autonomy in weapon systems can and will be gradual. Rejecting LAWS and focusing on PALWS for that reason does not mean that PALWS cannot be ethically problematic. It is not legitimizing them. Rather, their legitimacy depends on a number of criteria. The distinction offered by the committee simply reorients the discussion to center on the relevant category.

LAWS Are Not Acceptable

France has publicly renounced the use of fully autonomous lethal weapons, for both ethical and operational reasons, since 2013. In 2018, President Emmanuel Macron said he was categorically opposed to LAWS, to the extent they would abolish all accountability. He added, the decision to give the green light has to be made by a human being because you need someone to take responsibility for it. In May 2021, French Defense Minister Florence Parlyconfirmed that France says and will always say no to killer robots. France refuses to entrust the decision of life or death to a machine that would act in a fully autonomous way and would escape any human control.

Frances position on LAWS is in line with its closest allies. The U.S. Department of Defenses 2012 directive explicitly stated that their weapon systems should allow commanders and operators to exercise appropriate levels of human judgment in the use of force. This is, of course, another way to say they should not be fully autonomous. Similarly, the United Kingdom repeatedly expressed that it is not developing lethal autonomous weapons systems, and the operation of weapons systems by the UK armed forces will always be under human oversight and control. Many other states made similar remarks. This is indeed one of the few points of consensus in the U.N. debate on LAWS: in one way or another, everyone insists on retaining human control. No one wants a fully autonomous weapon, as full autonomy, literally the ability to set ones own rules, would mean unpredictability, which would make such systems militarily useless.

But this only begs a more difficult question: Should countries preventatively ban LAWS? This is where the disagreement lies.

The French Defense Ethics Committee also rejected incorporating LAWS into the countrys military for a number of reasons. LAWS would:

[B]reak the chain of command; run counter to the constitutional principle of having liberty of action to dispose of the armed forces; not provide any assurance as to compliance with the principles of international humanitarian law; be contrary to our military ethics and the fundamental commitments made by French soldiers, i.e. honour, dignity, controlled use of force and humanity.

The committee considered it legitimate and vital to continue research in the area of autonomy in lethal weapons, a research focused on ways and means of enabling French forces to counter the use of LAWS by states or other enemies, but without using LAWS ourselves.

PALWS Are Interesting and Risky

PALWS offer a number of advantages in terms of performance, precision, pertinence, protection, and permanence (the 5 Ps). In terms of performance, they will provide means to gain speed, in particular by shortening the observe-orient-decide-act loop. Also, one of the greatest challenges of the future of warfare will be defense against incoming conventional or nuclear strikes at hypersonic speed (of at least Mach 5, with some of them reportedly reaching Mach 20), leaving very little time to react and therefore requiring a greater autonomization. The same is true regarding defense against a saturation attack, or swarming. PALWS will also be useful to monitor very vast areas in all environments (land, air, sea, cyber, space) that cannot be covered without a certain degree of autonomy.

PALWS will also help to deal with the increasing mass of information (data deluge) that confront command centers and individual soldiers. Autonomous systems can help decision-making on an increasingly interconnected battlefield. They will also help penetrate highly defended areas physically and virtually; improve the precision of strikes; and protect soldiers, especially against improvised explosive devices or in contaminated environments. Finally, PALWS will last longer than human teams at sea, in the air, or on the ground, especially in dangerous or dirty environments, and they will therefore provide a greater permanence in a given area.

At the same time, PALWSs present a number of risks. Deploying autonomous weapons even if they are only partially autonomous tests the moral and social acceptability of using force without human intervention. Domestic opposition to the use of PALWS, including among the soldiers themselves, could undermine confidence in the states actions and legitimacy. Machine Learning may also lead to unexpected and unwanted behavior, as it raises issues on the long-term reliability of the systems.

There is also the issue of accountability: In the event of an incident (e.g., friendly fire or civilian casualties), who should be considered responsible? This is indeed one of the main criticisms directed at autonomous weapons and invoked by opponents as a reason to ask for a preventative ban. The integration of autonomy in weapon systems will inevitably make it more difficult to establish responsibility as there are many layers of control (state, manufacturer, programmer, system integrator, contractor, and military commander). Establishing responsibility will be difficult but not impossible, because an autonomous decision-making capacity does not break the causal chain allowing attribution and responsibility, as professor Marco Sassli explained in 2014. Moreover, such a dilution of responsibility is not unheard of, as it is already what happens when a plane on automatic pilot crashes, or when a self-driving car has an accident.

Among other risks of incorporating PALWS, the Defense Ethics Committee identified hacking (thereby hijacking those systems); the psychological impact on humans, especially those excluded from the decision-making process or no longer able to understand what the system is doing, potentially causing a lack of involvement or a loss of humanity in combat; and other psychological risks such as blindly trusting the machine, losing confidence in the human ability to deal with a complex situation, and developing all kinds of cognitive biases. There is also a risk of lowering the threshold of the use of force, and a risk of global proliferation, including acquisition by non-state actors.

How PALWS Could Be Ethically Acceptable

It is essential to delineate conditions under which it would be ethically acceptable to design, develop, and deploy PALWS. This is what the Committee called the 5Cs: command, risk control, compliance, competence, and confidence.

For each mission, PALWS should have rules set up by the human command (in terms of its target, spatial and temporal limits, rules of engagement, and other constraints); they should not be able to change those rules themselves (only human command can); they should not be able to assign a mission departing from what was initially programmed to another PALWS, or only after validation by the human command; and what they acquire through machine learning during a mission should not be used to program new tasks without human involvement.

Additionally, military personnel deploying PALWS (not only operators but also tactical leaders, theatre commanders and strategic leaders) should be prepared and trained accordingly. Similarly, any personnel involved in the design, development and promotion of those weapons (e.g., engineers, researchers, diplomats, politicians) should be made aware of the various risks and issues their use involve. Public authorities should be informed as well. Furthermore, mechanisms such as emergency deactivation or self-destruction should be implemented in the systems, in the event of a communication loss, as well as a device for aborting a mission in progress.

The French Defense Ethics Committee also recommended conducting a complete legal review whenever decision-making autonomy is developed in a lethal weapon system, especially as far as identification, classification and opening fire functions are concerned. Last but not least, it also advocated for international transparency.

Looking Ahead

There is nothing radically new in this French Defense Ethics Committee opinion for those closely following the decade-long, international debate on more or less autonomous weapons. Most, if not all, of these recommendations have been made by scholars and non-governmental organizations. What is interesting in this ethical opinion is that it also involves legal, scientific, and operational arguments, and that this comes from a committee set up by the French Ministry of Defense. However, what is at stake here is not just one state. The more individual states develop a clear and detailed public policy, the easier it will be to agree on a normative framework at the global level.

Jean-Baptiste Jeangene Vilmer, Ph.D., a member of the French Defense Ethics Committee, is the director of the Institute for Strategic Research (IRSEM) at the French Ministry of the Armed Forces, and a nonresident senior fellow at the Atlantic Council, Washington, D.C. He is also an adjunct professor at the Paris School of International Affairs (PSIA), Sciences Po, and an Honorary Ancien of the NATO Defense College. The views and opinions expressed in this article are the authors alone and do not necessarily reflect the official position of the French Defense Ethics Committee or the French Ministry of the Armed Forces.

Image: U.S. Navy

Read more here:
A French Opinion on the Ethics of Autonomous Weapons - War on the Rocks

Markeshaw Tiruneh G/Medhin,1 Endeshaw Chekol Abebe,2 Tekeba Sisay,3 Nega Berhane,3 Tesfahun Bekele Snr,1 Tadesse Asmamaw Dejenie1

1Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Biochemistry, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia; 3Institute of Biotechnology, College of Natural Science, University of Gondar, Gondar, Ethiopia

Correspondence: Markeshaw Tiruneh G/Medhin Tel +251922712112Email [emailprotected]

Abstract: Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins are referred to as CRISPR-Cas9. Bacteria and archaea have an adaptive (acquired) immune system. As a result, developing the best single regulated RNA and Cas9 endonuclease proteins and implementing the method in clinical practice would aid in the treatment of diseases of various origins, including lung cancers. This seminar aims to provide an overview of CRISPR-Cas9 technology, as well as current and potential applications and perspectives for the method, as well as its mechanism of action in lung cancer therapy. This technology can be used to treat lung cancer in two different ways. The first approach involves creating single directed RNA and Cas9 proteins and then distributing them to cancer cells using suitable methods. Single directed RNA looks directly at the lungs mutated epidermal growth factor receptor and makes a complementary match, which is then cleaved with Cas9 protein, slowing cancer progression. The second method is to manipulate the expression of ligand-receptors on immune lymphocytic cells. For example, if the CRISPR-Cas9 system disables the expression of cancer receptors on lymphocytes, it decreases the contact between the tumor cell and its ligand-receptor, thus slowing cancer progression.

Keywords: CRISPR, Cas9, CRISPR-Cas9 technology, cancer, lung cancer, cancer treatment

The word CRISPR-Cas9 refers to Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins.15 CRISPR-Cas9 system is a kind of acquired immunity possessed by most bacteria and archaea (prokaryotes) to act against their enemies (bacteriophages).4,6 It is a ribonucleic acid (RNA) guided, convenient, and versatile endonuclease platform for site-specific genome editing,1,7,8 which can play a tremendous role in the application of cancer therapy.1 The application of this technology can be used to resolve mutations and to introduce site-specific therapeutic genes in human cells so that, correcting disease-causing mutations, and alleviate disease-related symptoms. This system is also a useful tool for delineating molecular mechanisms involving hematological malignancies.4 Sequence-specific gene editing using CRISPR-Cas9 shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments like cancers.3,9 To accomplish its task, it requires Cas9 DNA endonuclease protein and single guided RNA (sgRNA) that can produce precise gene matching for editing and correction techniques.2 So the system has enabled easy manipulation of genes for the scientific community by making the hybrid to the target sequence and cleaving the double-strand DNA.10

Additionally, the CRISPR-Cas9 technology is increasingly feasible to overcome drug resistance in breast cancer therapy and will become an essential tool for personalized medicine.4 It is a technological breakthrough that facilitates the ability to change nucleic acids,11 and with continued improvement in the function, the system can help to develop best treatment options to a variety of genetic disease which affects several tissues in our body.12 Gene manipulation using CRISPR-Cas9 system has revolutionized and made it easy to study the work of genes and importantly opens the new era of treatment mechanisms for different disease conditions including cancer.13 Technologies like this are a simple and efficient method of targeting the required DNA regions.14 Thus, scientists have designed two main components of the system for easy detection and alteration of gene function one component is a protein Cas9 that enzymatically cleave the desired gene and the sgRNA which scans and determines where the gene of interest will be cleaved by Cas9 protein.3,12,15 The system has been scientifically optimized and developed to regulate expression of the gene, modify and edit the desired locus and this makes the technology of choice seen by the scientific community to treat or edit disease-causing mutations more efficiently than ever before. Furthermore, its application is encouraging for more vigorous gene therapy in clinical setups.16 Based on the discovery, there are three main types of CRISPR-Cas9 system (I to III) and with three additional types (IV to VI) being identified more recently.17 They are different during the processes of immunity, adaptation, expression, and interference, each type acts in distinct mechanisms to ensure genetic manipulation. Type I employs a large complex of Cas9 proteins with distinct helicase and DNase activities, while type III employs repeat-associated mysterious proteins, which form a large Cas9 superfamily. Another classification is based on subunit effectors, with multi-subunit effector complexes being the most common. Types I, III, and IV are grouped in class 1. Those systems, on the other hand, that have a single subunit effector are categorized as class 2 comprising types II, V, and VI.17,18 Type II uses only a Single protein (Cas9) for its nuclease activity and has got more attention and adopted for genome engineering.5,17,19 Thus, the objective of this seminar is to introduce CRISPR-Cas9 technology and describe current applications and future perspectives of the system with its mechanism of action on lung cancer therapy.

The tracrRNA gene will be transcribed to tracrRNA, the crRNA gene will be transcribed to pre crRNA, and the Cas9 gene will be transcribed to Cas9 messenger RNA and converted to Cas9 protein, all of which will be post-transcribed and chopped off to form the mature CRISPR-Cas9 complex.20 Cas1 and Cas2 integrase, which are present in all CRISPR forms, catalyze spacer integration on the CRISPR array especially on the leader end of the repeat there will be a nucleophilic attack of the 3 OH of the protospacers followed by the same practice on the spacer end of the repeat.21

The CRISPR-Cas9 method has a variety of formulation methods for genome editing. The use of a plasmid-based CRISPR-Cas9 system encoding both the Cas9 protein and sgRNA from the same vector, which is necessary to avoid multiple transfections of different components of the technology, is the leading and possibly the easiest technique. The Cas9 protein and sgRNA will be expressed in the vector, which will form the sgRNA-Cas9 complex within cells to edit the target genomic sequences.3,12,15,18 The second approach involves combining Cas9 mRNA and sgRNA. The sgRNA-Cas9 complex will be formed when Cas9 mRNA is converted into Cas9 protein in cells. The third strategy is to deliver the in vitro assembled sgRNA-Cas9 complex directly to the cell.18

It is difficult to transmit nucleic acid in general, and CRISPR-Cas9 in particular, to the target tissue or cell. Physical and vector (viral or non-viral) approaches are two of the most widely used distribution strategies.11,22,23 Electroporation and microinjections are used in physical methods, while viral delivery strategies such as adeno associated virus (AAV) are widely used in vector-based methods since they are not disease-causing agents and can infect both dividing and non-dividing cells25 and lentivirus with inactivated integrase enzymes are under investigation.24

Another technique is lipofection (lipid-mediated nanoparticle transfection), which is possibly the most efficient CRISPR-Cas9 in vivo delivery method.22 This technique was further developed by26 and is currently being tested in clinical trials.13,24

The CRISPR-Cas9 system, as discussed, a little earlier, is made up of two main components that work together to accomplish its goal.19 The sgRNA contains crRNA, which scans and identifies the target DNA sequences that must be cleaved and corrected, and transactivated crRNA (tracrRNA), which recruits component two, the Cas9 protein DNA endonuclease, which can sense, identify, and establish site-specific double-strand DNA breaks (DSB).15 Because of its simplicity and convenience, the bacterial type II CRISPR-Cas9 system has been used for RNA-guided engineering nucleases.4,18 However, the proto-spacer adjacent motifs (PAM) sequences are required by the method. After recognition, two Cas9 domains cleave double-stranded DNA: the endonuclease domain named for characteristic histidine and asparagine residues (HNH) domain, which cleaves the complementary strand, and the endonuclease domain named for an E. coli protein involved in DNA repair (RuvC-like) domain, which cleaves the non-complementary strand.17 As a result, the host DNA repair machinery introduces numerous mutations such as substitutions, deletions, and insertions in the target genome, including non-homologous end joining (NHEJ) or homologous-dependent repair (HDR).1518 Another paper, CRISPR-Cas9 for Cancer Therapy: Hopes and Challenges, supports this theory by demonstrating that the sgRNA-Cas9 complex scans and anneals to the genomic target sequence with base-pairing complementarity and precisely cleaves double-stranded DNA of the target cell after identification of the protospacer adjacent motif (PAM) sequence adjacent to the target sequence. NHEJ or HDR pathways are activated as a result of double-strand breaks. NHEJ is an error-prone repair mechanism that results in indels (insertions or deletions) of random base pairs disrupting the target sequence in the absence of a homologous repair prototype with more specific repair mechanisms.23,27

Lung cancer is the major cause of death in the United States and a significant public health concern worldwide.5 In both developed and developing countries, it is a common cause of morbidity and mortality.28 According to a study conducted by the American Lung Cancer Society in 2015, lung cancer claims the lives of almost 150,000 people each year. However, surgery and radiation were used as treatment options. The treatment was later changed to selective Tyrosine kinase inhibitors (TKIs) like gefitinib and erlotinib to inhibit the tyrosine kinase activity of epidermal growth factor receptor, which has technical difficulties and nonspecific cytotoxicity (EGFR).29,30 Extracellular ligand binding, transmembrane, and intracellular tyrosine kinase domains are found in this membrane glycoprotein. When the ligand activator binds to the extracellular ligand domain, it transduces and initiates intracellular kinase activities, which cause cellular proliferation, neovascularization, invasion, and metastasis, as well as reduced apoptosis and glycolysis activation. These medications, however, have encountered drug resistance.28,29

The CRISPR-Cas9 device is the start of a new biotechnological era and a groundbreaking technology that is being used to treat lung cancer.6,29 The system works in two ways. The first is by designing sgRNA that looks for the mutated EGFR sequence, which is then accompanied by Cas9 protein. To do so, scientists created a CRISPR device that has complementary sequences with the mutated EGFR and introduced it into the patient, as mentioned earlier which has complementary sequences with the mutated EGFR and introducing this into the patient. As this complementary sequence binds to the mutated EGFR, the Cas9 protein (endonuclease) creates a double-stranded or single-stranded DNA break, depending on the type of enzyme used, followed by DNA repair mechanisms such as homologous or non-homologous DNA repair.29 If the receptor mutation is limited, there will be no contact between the ligand activator, resulting in no cell proliferation, neovascularization, or cancer metastasis, and the problem will be solved. The inhibition of EGFR by CRISPR-Cas9 increases the expression of major histocompatibility complex class I, which improves cytotoxic lymphocyte recognition and lysis of tumor cells.30,31 Off-target effects, which can induce genome instability, gene functional disturbances, and epigenetic alterations, are a challenge. Off-target effects of CRISPR-Cas9 systems, particularly when used for therapeutic purposes, should be minimized and precisely profiled. Off-target effects are separated into two categories: off-target binding and off-target cleavage. Cas9 can bind to target sequences that are partially complementary to sgRNA and inhibit target gene transcription without cleaving them.8 Off-target binding effects may thus be removed in traditional off-target identification approaches, such as using in vitro assembled sgRNA with a long-lasting association with cas9, which also has a high proportion of on-target and high efficiency for genome editing. Another technique is to use a Cas9 variant or modified Cas9 that can generate a single nick at one strand.23 So that the off-target effect is reduced.

The second, and equally significant, strategy for using this biotechnological method to treat lung cancer is to search for immune cells like lymphocytes. T cells are immune cells that are extracted from the blood of patients engaged in a clinical trial for lung cancer treatment in China, and then CRISPR-Cas9 is used to knock out a gene in the cells that encodes a protein called PD-1. The edited gene cells would then be propagated in the lab before being injected back into the patients bloodstream.6,25 Scientists took blood from the patient and extracted lymphocytes, which were then treated with a CRISPR-Cas9 gene-editing system containing a sgRNA sequence with a pattern identical to lymphocytes programmable death 1 protein (PD 1). When the system detects its target sequence, cas9 would sever the DNA, which is then repaired by cell repair mechanisms. When the expression of the PD 1 gene is blocked or disabled, cancerous cells lack the receptor on immune lymphocytes.6,25 As a result, if lymphocytes do not express the PD 1 receptor well, there will be less contact between the cancerous ligand and receptor, causing the T cell receptor to identify the problematic cell and perform its function. Naturally, these manipulated lymphocytes were screened for viability and lympho-proliferation to rule out new mutations, and only those cells that passed the test were returned to the patient.6,25 Furthermore, knocking out the PD-1 protein on immune cells is necessary for caspase activation, which is needed for programmed cell death and enhanced apoptosis in cancerous cells.31 It also concludes that PD-1-deficient cells have potent antitumor activity of cytotoxic lymphocytes. The hyperactivity of the manipulated T cells is one of the technologys drawbacks for use in this way6 and obtaining a safe and efficient delivery method, as well as some side effects Patients with advanced NSCLC with positive PD-1 expression were assigned to a Phase I clinical trial to assess the safety of CRISPR-Cas9-mediated knockout of PD-1 gene therapy in patients with metastatic non-small cell lung cancer. Nine patients were enrolled, and eight patients received PD-1 deficient T cell therapy, and the patients were manifested with PD-1 deficient T cell therapy.25 Patients undergoing PD-1 deficient T cell therapy, on the other hand, appeared to be healthy, and researchers recommended that broader studies be conducted to determine the most appropriate dosage and immune response.

In cancer biology, the CRISPR-Cas9 device has a bright future ahead of it,9, because it is a technology that is adaptable, simple, convenient and efficient.32,33 The method introduces a novel approach to cancer treatment by allowing for modifications to the genome of target cells, which was previously difficult to achieve.3436 the technologys versatility, effectiveness, and flexibility would make it the best form of cancer care in the future.4,37,38 It will affect cancer biology as a whole in the future,34 and if researchers have devised well-organized strategies and instruments for delivering the technology to the target cell or tissue, as well as effective methods and instructions for controlling and eliminating the technologys off-target effects.

The CRISPR-Cas9 device is a recent biotechnological breakthrough and scientific achievement. This technology has created a new treatment option for diseases of various origins, such as cancer and infectious disease. To solve the problem, the best sgRNA must be designed using a CRISPR tool (http://crispr.mit.edu) and its associated endonuclease cas9 protein against the target sequence. However, ethical concerns, the need for the best delivery strategies, and the risk of off-target effects are only a few of the problems that must be addressed. Since the technology is still in its infancy, researchers must devise simple methods and mechanisms to track and test its protection and efficacy. For a simple comparison, the benefits of this technology are simple, fast, relatively effective, relatively precise, and versatile, while the drawbacks are distribution is difficult, ethical problems are highly conservative, some off-target effects, and some adverse effects.

ATP, Adenosine triphosphate; CRISPR, Clustered regularly interspaced short palindromic repeat; CRISPR-Cas, Clustered regularly interspaced short palindromic repeat-associated; CrRNA, Clustered regularly interspaced short palindromic repeat ribonucleic acid; DNA, Deoxyribonucleic acid; DSB, Double-stranded break; EGFR, epidermal growth factor receptor; HDR, Homologous directed repair; mRNA, Messenger ribonucleic acid; NHEJ, Non-homologous end-joining; PD 1, Programmable death protein 1; RNA, Ribonucleic acid; SgRNA, Single guided ribonucleic acid; TracrRNA, Trans activating clustered regularly short palindromic repeat ribonucleic acid; TKIs, Tyrosine kinase inhibitors.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

There is no funding to report.

The authors declare that they have no conflicts of interest for this work.

1. Liu T, Shen JK, Li Z, Choy E, Hornicek FJ, Duan Z. Development and potential applications of CRISPR-Cas9 genome editing technology in sarcoma. Cancer Lett. 2016;373(1):109118. doi:10.1016/j.canlet.2016.01.030

2. Yin H, Song CQ, Dorkin JR, et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016;34(3):328333. doi:10.1038/nbt.3471

3. Zhen S, Li X. Oncogenic human papillomavirus: application of CRISPR/Cas9 therapeutic strategies for cervical cancer. Cell Physiol Biochem. 2017;44(6):24552466. doi:10.1159/000486168

4. Chen Y, Zhang Y. Application of the CRISPR/Cas9 system to drug resistance in breast cancer. Adv Sci. 2018;5(6):1700964. doi:10.1002/advs.201700964

5. Shen Q, Li J, Mai J, et al. Sensitizing non-small cell lung cancer to BCL-xL-targeted apoptosis. Cell Death Dis. 2018;9(10):13. doi:10.1038/s41419-018-1040-9

6. Castillo A. Gene editing for the treatment of lung cancer (CRISPR-Cas9). Colomb Med. 2016;47(4):178180. doi:10.25100/cm.v47i4.2856

7. Platt RJ, Chen S, Zhou Y, et al. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell. 2014;159(2):440455. doi:10.1016/j.cell.2014.09.014

8. Wen WS, Yuan ZM, Ma SJ, Xu J, Yuan DT. CRISPRCas9 systems: versatile cancer modeling platforms and promising therapeutic strategies. Int J Cancer. 2016;138(6):13281336. doi:10.1002/ijc.29626

9. Bhattacharjee R, Purkayastha KD, Adapa D, Choudhury A. CRISPR/Cas9 genome editing system in the diagnosis and treatment of cancer. J RNAi Gene Silencing. 2017;13:585591.

10. Gwiazda KS, Grier AE, Sahni J, et al. High-efficiency CRISPR/Cas9-mediated gene editing in primary human T-cells using mutant adenoviral E4orf6/E1b55k helper proteins. Mol Ther. 2016;24(9):15701580. doi:10.1038/mt.2016.105

11. Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014;343(6166):8084. doi:10.1126/science.1246981

12. Ran FA, Cong L, Yan WX, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186191. doi:10.1038/nature14299

13. Gori JL, Hsu PD, Maeder ML, Shen S, Welstead GG, Bumcrot D. Delivery and specificity of CRISPR/Cas9 genome editing technologies for human gene therapy. Hum Gene Ther. 2015;26(7):443451. doi:10.1089/hum.2015.074

14. Shinmyo Y, Tanaka S, Tsunoda S, Hosomichi K, Tajima A, Kawasaki H. CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation. Sci Rep. 2016;6(1):13. doi:10.1038/srep20611

15. Ratan ZA, Son YJ, Haidere MF, et al. CRISPR-Cas9: a promising genetic engineering approach in cancer research. Ther Adv Med Oncol. 2018;10:1758834018755089. doi:10.1177/1758834018755089

16. Jamal M, Ullah A, Ahsan M, et al. Treating genetic disorders using state-of-the-art technology. Curr Issues Mol Biol. 2017;26:3346. doi:10.21775/cimb.026.033

17. Kim EJ, Kang KH, Ju JH. CRISPR-Cas9: a promising tool for gene editing on induced pluripotent stem cells. Korean J Intern Med. 2017;32(1):42. doi:10.3904/kjim.2016.198

18. Liu C, Zhang L, Liu H, Cheng K. Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications. J Control Release. 2017;266:1726. doi:10.1016/j.jconrel.2017.09.012

19. Snchez-Rivera FJ, Jacks T. Applications of the CRISPRCas9 system in cancer biology. Nat Rev Cancer. 2015;15(7):387393. doi:10.1038/nrc3950

20. Lino CA, Harper JC, Carney JP, Timlin JA. Delivering CRISPR: a review of the challenges and approaches. Drug Deliv. 2018;25(1):12341257. doi:10.1080/10717544.2018.1474964

21. McGinn J, Marraffini LA. Molecular mechanisms of CRISPRCas spacer acquisition. Nat Rev Microbiol. 2019;17(1):712. doi:10.1038/s41579-018-0071-7

22. Finn JD, Smith AR, Patel MC, et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 2018;22(9):22272235. doi:10.1016/j.celrep.2018.02.014

23. Martinez-Lage M, Puig-Serra P, Menendez P, Torres-Ruiz R, Rodriguez-Perales S. CRISPR/Cas9 for cancer therapy: hopes and challenges. Biomedicines. 2018;6(4):105. doi:10.3390/biomedicines6040105

24. Kolli N, Lu M, Maiti P, Rossignol J, Dunbar GL. Application of the gene-editing tool, CRISPR-Cas9, for treating neurodegenerative diseases. Neurochem Int. 2018;112:187196. doi:10.1016/j.neuint.2017.07.007

25. Lu Y. PD-1 knockout engineered T cells for metastatic non-small cell lung cancer. ClinicalTrials.gov. 2019. doi:10.1016/j.compcom.2006.05.002

26. Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020;578(7794):229236. doi:10.1038/s41586-020-1978-5

27. Pandey VK, Tripathi A, Bhushan R, Ali A, Dubey PK, Therapy G. Application of CRISPR/Cas9 genome editing in genetic disorders: a systematic review up to date. J Genet Syndr Gene Ther. 2017;8(2). doi:10.4172/2157-7412.1000321

28. Jiang C, Lin X, Zhao Z. Applications of CRISPR/Cas9 technology in the treatment of lung cancer. Trends Mol Med. 2019;25(11):10391049. doi:10.1016/j.molmed.2019.07.007

29. Tang H, Shrager JB. CRISPR/Casmediated genome editing to treat EGFRmutant lung cancer: a personalized molecular surgical therapy. EMBO Mol Med. 2016;8(2):8385. doi:10.15252/emmm.201506006

30. Lizotte PH, Hong RL, Luster TA, et al. A high-throughput immune-oncology screen identifies EGFR inhibitors as potent enhancers of antigen-specific cytotoxic T-lymphocyte tumor cell killing. Cancer Immunol Res. 2018;6(12):15111523. doi:10.1158/2326-6066.CIR-18-0193

31. Zhao Z, Shi L, Zhang W, et al. CRISPR knock out of programmed cell death protein 1 enhances the anti-tumor activity of cytotoxic T lymphocytes. Oncotarget. 2018;9(4):5208. doi:10.18632/oncotarget.23730

32. Zhang B. CRISPR/Cas gene therapy. J Cell Physiol. 2021;236(4):24592481.

33. Lu Y, Xue J, Deng T, et al. Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer. Nat Med. 2020;26(5):732740. doi:10.1038/s41591-020-0840-5

34. Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances, and prospects. Signal Transduct Target Ther. 2020;5(1):123.

35. Xu M, Weng Q, Ji J. Applications and advances of CRISPR/Cas9 in an animal cancer model. Brief Funct Genomics. 2020;19(3):235241. doi:10.1093/bfgp/elaa002

36. Ma CC, Wang ZL, Xu T, He ZY, Wei YQ. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv. 2020;40:107502. doi:10.1016/j.biotechadv.2019.107502

37. Hanna RE, Doench JG. Design and analysis of CRISPRCas experiments. Nat Biotechnol. 2020;38(7):813823. doi:10.1038/s41587-020-0490-7

38. Hong W, Huang M, Wei Y, Wei X. A new and promising application of gene editing: CRISPR-controlled smart materials for tissue engineering, bioelectronics, and diagnostics. Sci China Life Sci. 2019;62(11):15471549. doi:10.1007/s11427-019-1576-0

Read more from the original source:
Crispr-cas9 for the treatment of lung cancer | BTT - Dove Medical Press

8 of 11 Patients in Dose Escalation Cohorts 2 and 3 Achieved Objective Response

6 of 11 Patients Achieved Complete Response, including 2 Patients Previously Treated with Autologous CD19 CAR T-cell Therapy

Favorable FT516 Safety Profile Was Observed; No FT516-related Serious Adverse Events or FT516-related Grade 3 or Greater Adverse Events

Outpatient Treatment Regimen Was Well-tolerated; No Events of Any Grade of Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, or Graft-vs-Host Disease

SAN DIEGO, June 04, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim Phase 1 data from the Companys FT516 program for patients with relapsed / refractory B-cell lymphoma at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting being held virtually June 4-8, 2021. FT516 is the Companys universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The ongoing Phase 1 dose-escalation study of FT516 is currently enrolling patients in the fourth dose cohort of 900 million cells per dose.

As of the data cutoff date of March 11, 2021, four patients in the second dose cohort of 90 million cells per dose and seven patients in the third dose cohort of 300 million cells per dose were evaluable for assessment of safety and efficacy. Eight of eleven patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria (see Table 1). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy.

These additional data from our Phase 1 study of FT516 administered off-the-shelf in the outpatient setting continue to reinforce its differentiated safety profile and underscore its potential clinical benefit, said Wayne Chu, M.D., Senior Vice President of Clinical Development of Fate Therapeutics. Based on the favorable therapeutic profile of FT516 that continues to emerge and the potential to treat patients on-demand without delay, we plan to initiate multiple indication-specific, dose-expansion cohorts for patients with B-cell lymphomas to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including those used as standard-of-care in earlier-line settings.

The ongoing Phase 1 clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single-dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting.

Safety DataNo dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events (TEAEs) of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were reported by investigators (see Table 2). All Grade 3 or greater TEAEs were consistent with lympho-conditioning chemotherapy and underlying disease. Of note, a Grade 3 or greater TEAE of infection was reported in one patient only. There were no discontinuations due to adverse events, and no patients withdrew from the study except in the setting of disease progression. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without the need for patient matching.

Activity DataAs of the data cutoff date of March 11, 2021, eleven relapsed / refractory patients in the second and third dose cohorts were evaluable for assessment of safety and efficacy. Of the eleven patients, nine patients completed both FT516 treatment cycles and eight patients achieved an objective response, including six patients who achieved a complete response, as assessed by PET-CT scan per Lugano 2014 criteria. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. Two patients showed progressive disease following the first FT516 treatment cycle and discontinued treatment. The Company previously reported that two patients treated in the first dose cohort (30 million cells per dose) showed progressive disease.

Patient Case StudyThe ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. Subsequent to the data cutoff date of March 11, 2021, the patient completed a second FT516 treatment cycle after which the response assessment continued to show complete response.

As of March 11, 2021 database entry. Data subject to source document verification.CR = Complete Response; PR = Partial Response; PD = Progressive DiseaseCAR = Chimeric antigen receptor; DH/DE = Double-hit / double expressor; DLBCL = Diffuse large B-cell lymphoma; FL = Follicular lymphoma; Gr = Grade; HGBCL = High-grade B-cell lymphoma; iNHL = Indolent non-Hodgkin lymphoma; TH = Triple-hit; Transformed iNHL = Aggressive B-cell lymphoma transformed from indolent non-Hodgkin lymphoma1 Cycle 2 Day 29 protocol-defined response assessment per Lugano 2014 criteria2 Subject did not proceed to Cycle 23 Confirmed DLBCL (transformation from Gr3A FL) subsequent to the data cutoff date of March 11, 20214 Cycle 2 Day 29 protocol-defined response assessment reported subsequent to the data cutoff date of March 11, 2021

CRS = Cytokine Release Syndrome; DL = Dose Level; GvHD = Graft vs. Host Disease; ICANS = Immune Cell-Associated Neurotoxicity Syndrome;M = Million; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event1 Includes two subjects in the first dose cohort of 30 million cells per dose

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Companys iPSC-derived NK cell product candidates, including FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT516. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

Here is the original post:
Fate Therapeutics Highlights Positive Interim Data from its Phase 1 Study of FT516 in Combination with - GlobeNewswire

Dear Editor

In our cuntry, Cuba, the phase II clinical trial of the vaccine candidate Abdala (CIGB 66), developed by the Center for Genetic Engineering and Biotechnology (CIGB), began this Monday, February 1st, at the Saturnino Lora Hospital, in the city of Santiago de Cuba. The results of the phase I study, which began on December 7, showed that the safety and reactogenicity profile of the immunogen was favorable for the two doses of the vaccine candidate studied, which made it possible to accelerate the start of this new stage.

Over the next few weeks, about 760 volunteers will be immunized, with the particularity that in this second phase, in addition to individuals between 19 and 54 years of age (Phase I), volunteers up to 80 years of age will be included. Individuals with a comorbidity or chronic disease may participate, as long as it is controlled. This is a clinical trial that is carried out randomly and totally blind, comparing the results of the vaccine candidate with the administration of placebo.

It is considered that all individuals will benefit because, once the codes are opened, those who received placebo will be vaccinated with the immunogen. If the safety and immunogenicity results are corroborated, this phase II will be evaluated in March (the trial must conclude by March 15), and it will be preparing rapidly to consider a phase III. It is found in the two doses evaluated that a high percent of individuals developed an antibody response against the SARS-CoV-2 protein, that the sera of these individuals had the ability to inhibit the binding of the receptor and that protein, and that these antibodies in addition, in a viral neutralization assay they also had functional activity.

Original post:
Development of the Abdala Vaccine Candidate in Cuba. - The BMJ

In early January 2021, a consultation was launched that asks whether organisms produced by genetic engineering should continue to be classified as genetically modified, if the organisms could have been developed using traditional breeding methods.

The consultation is especially focused on gene editing, also known as genome editing, a technology that allows scientists to add, remove or alter an organisms DNA.

Unlike older types of transgenic genetic modification, this process doesnt introduce foreign DNA into the gene. In a speech launching the consultation, Environment Secretary George Eustice said gene editing raises far fewer ethical or biological concerns than transgenic modification and respects the rules of nature.

In 2018, the European Court of Justice ruled that gene-edited crops should be considered the same as other genetically modified crops under EU law, a ruling Eustice called flawed and stifling to scientific progress.

Prime Minister Boris Johnson shares a similar view. In 2019 he pledged to liberate the UKs extraordinary bioscience sector from anti-genetic-modification rules.

Read more about gene editing:

Gene editing is a relatively new and fast-evolving technology. The first type of gene editing, using CRISPR/Cas9, was only developed in 2012 (the two women that developed it won the 2020 Nobel Prize in Chemistry).

Views on regulating the use of gene editing in producing genetically modified animals or crops have generally fallen into two camps, says Prof Katherine Denby from the University of York, who works on new ways to improve crops using tools such as gene editing.

The first camp argues that as gene-edited crops or livestock could have arisen through traditional breeding processes, they should not be classed as genetically modified organisms, meaning they wouldnt be subject to genetic modification regulations.

The second camp holds that any organism made through gene editing should be regulated as a genetically modified organism, regardless of whether the final product could have been made using traditional breeding. Countries such as the US, Australia and Japan have taken the former, more relaxed, approach, while the EU has taken the latter, more stringent one.

Current UK regulations mean gene-edited crops can technically come to market, but the regulatory process is both lengthy and extremely costly, says Denby.

Its really prohibiting the development of products, both crops and genome-edited livestock, just because of that cost, she says. This, in turn, is prohibiting the development of traits that are for public good, such as disease resistance, she says.

Gene editing could potentially offer greater food security for the UK, but are there unseen dangers? Getty Images

For example, her own work aims to replicate the disease resistance found in older and wild relatives of lettuce in more modern varieties, a process that will go many times faster using gene editing rather than traditional breeding.

But other scientists are more sceptical about the benefits that gene editing can bring and are concerned about its potential dangers.

This technology comes with innate risks to alter the genetic composition, the patterns of gene function, says Dr Michael Antoniou, head of the gene expression and therapy group at Kings College London. In doing so you change the plants biochemistry.

Antoniou says gene editing is not as highly precise as is often claimed and can bring about unintended mutations. Worryingly, those who are developing gene-edited crops and foods are ignoring the risks, he says.

For instance, gene editing could run the risk of producing novel toxins or allergens, or increasing the levels of pre-existing toxins and allergens, especially in plants, he says.

Without strict safety checks, its possible that crops that are potentially harmful could enter the marketplace unlabelled and would therefore also be difficult to trace if any adverse outcomes were to be found, he adds.

In Antonious view, gene editing is unquestionably a genetic modification procedure and should continue being regulated in the UK as it is in the EU.

But many scientists argue that gene editing is crucial to supporting a more sustainable food system.

Genome editing is already used in medicine and has immense potential for tackling major agricultural challenges related to food security, climate change and sustainability, says Prof Denis Murphy from the University of South Wales.

Read more fromReality Check:

Denby agrees and says gene editing can play a part in making the UKs food system more sustainable, healthy and affordable, while admitting its not going to be a magic bullet.

But for Antoniou the focus really needs to be on the agricultural system as a whole, rather than improving individual crops and seeds.

Gareth Morgan, head of farming and land use policy at the Soil Association, has called gene editing a sticking plaster that diverts vital investment and attention from other more effective solutions.

The focus needs to be on how to restore exhausted soils, improve diversity in cropping, integrate livestock into rotations and reduce dependence on synthetic nitrogen and pesticides, he says. We want to see immediate progress in these areas rather than using Brexit to pursue a deregulatory agenda for genetic modification.

Visit the BBCs Reality Check website at bit.ly/reality_check_ or follow them on Twitter@BBCRealityCheck

Read more here:
Gene editing: Should livestock and crops be genetically engineered in the UK? - BBC Focus Magazine