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New genetic tools will deliver improved farmed fish, oysters, and shrimp. Here’s what to expect – Science Magazine

Posted: November 20, 2020 at 3:57 pm

At research pens in Chile researchers develop strains of farmed Atlantic salmon with improved traits such as growth and health.

By Erik StokstadNov. 19, 2020 , 2:00 PM

Two years ago, off the coast of Norway, the blue-hulled Ro Fjell pulled alongside Ocean Farm 1, a steel-netted pen the size of a city block. Attaching a heavy vacuum hose to the pen, the ships crew began to pump brawny adult salmon out of the water and into a tank below deck. Later, they offloaded the fish at a shore-based processing facility owned by SalMar, a major salmon aquaculture company.

The 2018 harvest marked the debut of the worlds largest offshore fish pen, 110 meters wide. SalMars landmark facility, which dwarfs the typical pens kept in calmer, coastal waters, can hold 1.5 million fishwith 22,000 sensors monitoring their environment and behaviorthat are ultimately shipped all over the world. The fish from Ocean Farm 1 were 10% larger than average, thanks to stable, favorable temperatures. And the deep water and strong currents meant they were free of parasitic sea lice.

Just a half-century ago, the trade in Atlantic salmon was a largely regional affair that relied solely on fish caught in the wild. Now, salmon farming has become a global business that generates $18 billion in annual sales. Breeding has been key to the aquaculture boom. Ocean Farm 1s silvery inhabitants grow roughly twice as fast as their wild ancestors and have been bred for disease resistance and other traits that make them well suited for farm life. Those improvements in salmon are just a start: Advances in genomics are poised to dramatically reshape aquaculture by helping improve a multitude of species and traits.

Genetic engineering has been slow to take hold in aquaculture; only one genetically modified species, a transgenic salmon, has been commercialized. But companies and research institutions are bolstering traditional breeding with genomic insights and tools such as gene chips, which speed the identification of fish and shellfish carrying desired traits. Top targets include increasing growth rates and resistance to disease and parasites. Breeders are also improving the hardiness of some species, which could help farmers adapt to a shifting climate. And many hope to enhance traits that please consumers, by breeding fish for higher quality fillets, eye-catching colors, or increased levels of nutrients. There is a paradigm shift in taking up new technologies that can more effectively improve complex traits, says Morten Rye, director of genetics at Benchmark Genetics, an aquaculture breeding company.

After years of breeding, Atlantic salmon grow faster and larger than their wild relatives.

Aquaculture breeders can tap a rich trove of genetic material; most fish and shellfish have seen little systematic genetic improvement for farming, compared with the selective breeding that chickens, cattle, and other domesticated animals have undergone. Theres a huge amount of genetic potential out there in aquaculture species thats yet to be realized, says geneticist Ross Houston of the Roslin Institute.

Amid the enthusiasm about aquacultures future, however, there are concerns. Its not clear, for example, whether consumers will accept fish and shellfish that have been altered using technologies that rewrite genes or move them between species. And some observers worry genomic breeding efforts are neglecting species important to feeding people in the developing world. Still, expectations are high. The technology is amazing, its advancing very quickly, the costs are coming down, says Ximing Guo, a geneticist at Rutgers University, New Brunswick. Everybody in the field is excited.

Fish farmingmay not have roots as old as agriculture, but it dates back millennia. By about 3500 years ago, Egyptians were raising gilt-head sea bream in a large lagoon. The Romans cultivated oysters. And carp have been grown and selectively bred in China for thousands of years. Few aquaculture species, however, saw systematic, scientific improvement until the 20th century.

One species that has received ample attention from breeders is Atlantic salmon, which commands relatively high prices. Farming began in the late 1960s, in Norway. Within 10 years, breeding had helped boost growth rates and harvest weight. Each new generation of fishit takes salmon 3 to 4 years to maturegrows 10% to 15% faster than its forebears. My colleagues in poultry can only dream of these kinds of percentages, says Robbert Blonk, director of aquaculture R&D at Hendrix Genetics, an animal breeding firm. During the 1990s, breeders also began to select for improved disease resistance, fillet quality, delayed sexual maturation (which boosts yields), and other traits.

Another success story involves tilapia, a large group of freshwater species that doesnt typically bring high prices but plays a key role in the developing world. An international research center in Malaysia, now known as WorldFish, began a breeding program in the 1980s that quickly doubled the growth rate of one commonly raised species, Nile tilapia. Breeders also improved its disease resistance, a task that continues because of the emergence of new pathogens, such as tilapia lake virus.

Genetically improved farmed tilapia was a revolution in terms of tilapia production, says Alexandre Hilsdorf, a fish geneticist at the University of Mogi das Cruzes in Brazil. China, a global leader in aquaculture production, has capitalized on the strain, building the worlds largest tilapia hatchery. It raises billions of young fish annually.

Now, aquaculture supplies nearly half of the fish and shellfish eaten worldwide (see chart, below), and production has been growing by nearly 4.5% annually over the past decadefaster than most sectors of the farmed food sector. That expansion has come with some collateral damage, including pollution from farm waste, heavy catches of wild fish to feed to penned salmon and other species, and the destruction of coastal wetlands to build shrimp ponds. Nevertheless, aquaculture is now poised for further acceleration, thanks in large part to genomics.

Aquaculture is rivaling catches from wild fisheries and is projected to increase. Much of the growth comes from freshwater fish in Asia, such as grass carp, yet most research has focused on Atlantic salmon and other high-value species. Genomic technology is now spreading to shrimp and tilapia.

(GRAPHIC) N. DESAI/SCIENCE; (DATA, TOP TO BOTTOM) FOOD AND AGRICULTURE ORGANIZATION OF HE UNITED NATIONS; HOUSTON et al., NATURE REVIEWS GENETICS 21, 389 (2020)

Breeders are most excited about a technique called genomic selection. To grasp why, it helps to understand how breeders normally improve aquaculture species. They start by crossing two parents and then, out of hundreds or thousands of their offspring, select individuals to test for traits they want to improve. Advanced programs make hundreds of crosses in each generation and choose from the best performing families for breeding. But some tests mean the animal cant later be used for breeding; measuring fillet quality is lethal, for instance, and screening for disease resistance means the infected individual must remain quarantined. As a result, when researchers identify a promising animal, they must pick a sibling to use for breedingand hope that it performs just as well. You dont know whether theyre the best of the family or the worst,says Dean Jerry, an aquaculture geneticist at James Cook University, Townsville, who works with breeders of shrimp, oysters, and fish.

With genomic selection, researchers can identify siblings with high-performance traits based on genetic markers. All they need is a small tissue samplesuch a clipping from a finthat can be pureed and analyzed. DNA arrays, which detect base-pair changes called single nucleotide polymorphisms (SNPs), allow breeders to thoroughly evaluate many siblings for multiple traits. If the pattern of SNPs suggests that an individual carries optimal alleles, it can be selected for further breeding even if it hasnt been tested. Genomic analyses also allow breeders to minimize inbreeding.

Cattle breeders pioneered genomic selection. Salmon breeders adopted it a few years ago, followed by those working with shrimp and tilapia. There is a big race from industry to implement this technology, says geneticist Jos Yez of the University of Chile, who adds that even small-scale producers are now interested in genetic improvement. As a rough average, the technique increases selection accuracy and the amount of genetic improvement by about 25%, Houston says. It and other tools are helping researchers pursue goals such as:

This trait improves the bottom line, allowing growers to produce more frequent and bigger hauls. Growth is highly heritable and easy to measure, so traditional breeding works well. But breeders have other tactics for boosting growth, including providing farmers with fish of a single sex. Male tilapia, for example, can grow significantly faster than females. Another strategy is to hybridize species. The dominant farmed catfish in the United States, a hybrid of a female channel catfish and a male blue catfish, grows faster and is hardier.

Inducing sterility stimulates growth, too, and has helped raise yields in shellfish, particularly oysters. In the 1990s, Guo and Standish Allen, now at the Virginia Institute of Marine Science, figured out a new way to create triploid oysters, which are infertile because they have an extra copy of each chromosome. These oysters dont devote much energy to reproduction, so they reach harvest size sooner, reducing exposure to disease. (When oysters reproduce, more than half their body consists of sperm or eggs, which no one wants to eat.)

Looking ahead, researchers are exploring gene transfer or gene editing to further enhance gains. And one U.S. company, AquaBounty, is just beginning to sell the worlds first transgenic food animal, an Atlantic salmon, that it claims is 70% more productive than standard farmed salmon. But the fish is controversial and has faced consumer resistance and regulatory hurdles.

Disease is often the biggest worry and expense for aquaculture operations. In shrimp, outbreaks can slash overall yield by up to 40% annually and can wipe out entire operations. Vaccines can prevent some diseases in fish, but not invertebrates, because their adaptive immune systems are less developed. So, for all species, resistant strains are highly desirable.

To improve disease resistance, researchers need a rigorous way to test animals. Thanks to a collaboration with fish pathologists at the U.S. Department of Agriculture (USDA), Benchmark Genetics was able to screen tilapia for susceptibility to two major bacterial diseases by delivering a precise dose of the pathogen and then measuring the response. They identified genetic markers correlated with infection and used genomic selection to help develop a more resistant strain. USDA scientists have also worked with Hendrix Genetics to increase the survival of trout exposed to a different bacterial pathogen from 30% to 80% in just three generations.

The fecundity of most aquatic species, like this trout (left), helps breeding efforts. Salmon eggs, 0.7 millimeters wide (right), are robust and easy for molecular biologists to work with.

Perhaps the most celebrated success has been in salmon. After researchers discovered a genetic marker for resistance to infectious pancreatic necrosis, companies quickly bred strains that can survive this deadly disease. Oyster breeders, meanwhile, have had success in developing strains resistant to a strain of herpes that devastated the industry in France, Australia, and New Zealand.

A big problem for Atlantic salmon growers is the sea louse. The tiny parasite clings to the salmons skin, inflicting wounds that damage or kill fish and make their flesh worthless. Between fish losses and the expense of controlling the parasites, lice cost growers more than $500 million a year in Norway alone. Lice are attracted to fish pens and can jump to wild salmon that pass by.

For years farmers have relied on pesticides to fight lice, but the parasite has become resistant to many chemicals. Other techniques, such as pumping salmon into heated water, which causes the lice to drop off, can stress the fish.

Researchers have found that some Atlantic salmon are better than others at resisting lice, and breeders have been trying to improve this trait. So far, theyve had modest success. Better understanding why several species of Pacific salmon are immune to certain lice could lead to progress. Scientists are exploring whether sea lice are attracted to certain chemicals released by Atlantic salmon; if so, its possible these could be modified with gene editing.

No sex on the farm. Thats a goal with many aquaculture species, because reproduction diverts energy from growth. Moreover, fertile fish that escape from aquaculture operations can cause problems for wild relatives. When wild fish breed with their domesticated cousins, for instance, the offspring are often less successful at reproducing.

Salmon can be sterilized by making them triploid, typically by pressurizing newly fertilized embryos in a steel tank when the chromosomes are replicating. But this can have side effects, such as greater susceptibility to disease. Anna Wargelius, a molecular physiologist at Norways Institute of Marine Research, and colleagues have instead altered the genes of Atlantic salmon to make them sterile, using the genome editor CRISPR to knock out a gene calleddeadend. In 2016, they showed that these fish, though healthy, lack germ cells and dont sexually mature. Now, theyre working on developing fertile broodstock that produce these sterile offspring for hatcheries. Embryos with the knocked-out genes should develop into fertile adults if injected with messenger RNA, according to a paper the group published last month inScientific Reports. When these fish mature later in December, they will try to breed them. It looks very promising, Wargelius says.

Another approach would not involve genetic modifications. Fish reproductive physiologists Yonathan Zohar and Ten-Tsao Wong of the University of Maryland, Baltimore County, are using small molecule drugs to disrupt early reproductive development so that fish mature without sperm or eggs.

Cooks and diners hate bones. Nearly half of the top species in aquaculture are species of carp or their relatives, which are notorious for the small bones that pack their flesh. These bones cant be easily removed during processing, so you cant just get a nice, clean fillet, says Benjamin Reading, a reproductive physiologist at North Carolina State University.

Researchers are studying the biology of these fillet bones to see whether they might one day be removed through breeding or genetic engineering. A few years ago, Hilsdorf heard that a Brazilian hatchery had discovered mutant brood stock of a giant Amazonian fish, the widely farmed tambaqui, that lacked these fillet bones. After trying and failing to breed a boneless strain, hes studying tissue samples from the mutants for clues to their genetics.

Geneticist Ze-Xia Gao of Huazhong Agricultural University is focusing on blunt snout bream, a carp that is farmed in China. Guided by five genetic markers, she and colleagues are breeding the bream to have few fillet bones. It could take 8 to 10 years to achieve, she says. They have also had some success with gene editingtheyve identified and knocked out two genes that control the presence of fillet bonesand they plan to try the approach in other carp species. I think it will be feasible, Gao says.

Aquaculture projects worldwide are hustling to domesticate new speciesa kind of gold rush rare in terrestrial farming. In New Zealand, researchers are domesticating native species because they are already adapted to local conditions. The New Zealand Institute for Plant and Food Research began to breed the Australasian snapper in 2004. Early work concentrated on simply getting the fish to survive and reproduce in a tank. One decade later, researchers started to breed for improved growth, and theyve since increased juvenile growth rates by 20% to 40%.

Genomic techniques have proved critical. Snapper are mass spawners, so it was hard for breeders to identify the parents of promising offspring, which is crucial for optimizing selection and avoiding inbreeding. DNA screening solved that problem, because the markers reveal ancestry. The institute is also breeding another local fish, the silver trevally, aiming for a strain that will reproduce in captivity without hormone implants. Its a long-term effort to breed a wild species to make it suitable for aquaculture, says Maren Wellenreuther, an evolutionary geneticist at the New Zealand institute and the University of Auckland.

These breeding effortsrequire money. Despite the growth of aquaculture, the fields research funding lags the amounts invested in livestock, although some governments are boosting investments.

Looking globally, geneticist Dennis Hedgecock of Pacific Hybreed, a small U.S. company that is developing hybrid oysters, sees a huge disparity between breeding investment in developed countrieswhich produce a fraction of total harvests but have the biggest research budgetsand the rest of the world. Simply applying classical breeding techniques could rapidly improve production, especially in the developing world, he says. Yet the hundreds of species now farmed could overwhelm breeding programs, especially those aimed at enhancing disease resistance, Hedgecock adds. The growth and the production is outstripping the scientific capability of dealing with the diseases, he says, adding that a focus on fewer species would be beneficial.

For genomics to help, experts say costs must continue to come down. One promising development in SNP arrays, they note, is a technique called imputation, in which cheaper arrays that search for fewer genetic changes are combined with a handful of higher cost chips that probe the genome in more detail. Such developments suggest genomic technology is at a pivot point where youre going to see it used broadly in aquaculture, says John Buchanan, president of the Center for Aquaculture Technologies, a contract research organization.

Many companies are already planning for larger harvests. SalMar will decide next year whether it will order a companion to Ocean Farm 1. It has already drawn up plans for a successor that can operate in the open ocean and would be more than twice the size, big enough to hold 3 million to 5 million salmon at a time.

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Genetic engineering research is a secret: How the federal government and the EU want to let us run blindly into a high-risk adventure – Pressenza,…

Posted: November 20, 2020 at 3:57 pm

Classified information: Millions and millions are spent on genetic engineering projects, but research into the risks of genome changes and into detection methods that make it possible to detect genetically modified organisms, for example in food, is completely underfunded.

Genetic engineering on the plate or in the field: Most people reject that. The nature awareness study is a regular survey of how citizens feel about environmental protection, nature and food security. For years, a very clear majority of those surveyed have been in favor of the fact that foods must be clearly labeled if they contain genetically modified organisms. Farmers for feed and seeds are also calling for this. And more than 80 percent of those surveyed generally reject genetic engineering in food.

The federal government now had to admit with great reluctance that tax money is generously distributed for research into new genetic engineering processes, while research funding on risks or detection methods is skimpy. Harald Ebner, spokesman for the Greens for genetic engineering policy, sums it up: While the federal government is nurturing research on new genetic engineering processes such as CRISPR / Cas & Co( (Clustered Regularly Interspaced Short Palindromic Repeats) with more than 27 million euros, detection and risk research is currently in progress times 2 million available! This reveals a huge imbalance to the detriment of environmental and health care and to the detriment of the enforcement of the rule of law . Such one-sided research funding in an area that is massively funded by the biotechnology industry itself is in clear contradiction to the governments consumer protection mandate, emphasizes Harald Ebner.

The crux of the matter is: So far there are hardly any detection methods with which a gene change that was carried out using methods of the new genetic engineering can be determined. Labeling is therefore only possible if the manufacturer expressly indicates this. Contamination, however, would not be noticed during controls. And this despite the fact that new genetic engineering methods are already being used in the fields of seeds and animal feed. Nevertheless, the federal government is saving funding for research into detection methods not to mention risk research. So were walking blindly into a genetic engineering adventure.

No wonder the federal government initially classified this information as classified, i.e. secret not to be published!

More on this and a more comprehensive statement in the background here:

Regarding genetic engineering in agriculture and nutrition (so-called agro-genetic engineering), the EU applies that organisms such as seeds, plants, animals, or even feed and, of course, especially food must be labeled if they contain genetically modified organisms or if such animal feed has been used. This is to protect the freedom of choice of farmers and consumers. The European Court of Justice ruled in 2018 that this labeling requirement also expressly applies to methods of new genetic engineering, such as CRISPR/Cas&Co. There is a catch: Up to now, there have hardly been any detection procedures for organisms that have been modified using the methods of the new genetic engineering, so that labeling cannot be carried out safely.

The EU Commission was commissioned to promote relevant evidence research and to present a study by April 2021 on the status of the research. In order to be able to offer this study, the EU Commission has sent a questionnaire with relevant questions about research and research funding to each individual member state.

Harald Ebner, spokesman for the Green Group for genetic engineering policy, has sent a so-called written question to the federal government on exactly this state of research and research funding in Germany. The answer came and is very informative but it was classified as classified, i.e. secret, not for publication. If the federal government really wants to conduct the discourse with the citizens on the new methods of genetic engineering seriously and objectively, it should also pour pure wine for the consumer, explains Harald Ebner and refers to the concerns of the citizens if there are possible consequences of genetically modified plants and animals.

Precisely because, the overwhelming majority in this country rejects genetic engineering, from field to fork, transparency, for example, about the use of taxpayers money to promote research in this area, is the top priority. Otherwise one could already get the impression that information is to be hidden that contradicts the will of consumers for a comprehensive technical impact assessment in dealing with the new genetic engineering methods.

It was only through a parliamentary procedure, a minor inquiry, that the answer from the federal government, more precisely from the Federal Ministry of Food and Agriculture, was now public.

Harald Ebner MdB, spokesman for genetic engineering and bioeconomy policy, explains the answer from the federal government, which has now finally become publicly available:

The answer proves what we have been criticizing for years: while the federal government is nurturing research on new genetic engineering processes such as CRISPR / Cas & Co with over 27 million euros, just 2 billion euros are available for detection and risk research. This reveals a huge imbalance to the detriment of environmental and health care and to the detriment of the enforcement of the rule of law. Such one-sided research funding in an area that is massively funded by the biotechnology industry itself is in clear contradiction to the governments consumer protection mandate. What is fatal is that the federal government itself has to admit that the inspection and control of organisms that have been produced by new genetic engineering processes would only be possible if detection methods were available. The federal government must protect the freedom of choice of farmers and consumers and ensure that genetic engineering law is implemented. What is urgently needed now is an immediate program for the promotion of detection methods and risk research in order to finally provide the still-young technology with an appropriate technology impact assessment. It is also noteworthy that the federal government, of all people, is dispelling the myth that the new genetic engineering could open up business areas for many small and medium-sized breeding companies. Because that is by no means the case: The Federal Government assumes that, just as with the old genetic engineering, there will also be concentration processes on the market with organisms that have been produced using new methods.

Press releasefrom Harald Ebner Member of the Bundestag

Translation by Lulith V., from the voluntary Pressenza translation team. We are looking for volunteers!

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Genetic engineering research is a secret: How the federal government and the EU want to let us run blindly into a high-risk adventure - Pressenza,...

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Genetic Engineering Market by Manufacturers, Regions, Type and Application, Forecast To 2026 New England Biolabs, Integrated DNA Technologies,…

Posted: November 20, 2020 at 3:57 pm

The latest research report on the Genetic Engineering Market Industry Analysis, Market Size, Opportunities and Forecast, 2020 2028 provides a comprehensive assessment of the Genetic Engineering market for the forecast period from 2020 to 2028, including market values for the years 2018 and 2019. The investigative report provides a detailed analysis of the impact of COVID-19 on various segments in the Genetic Engineering market based on product type, application, and end-use across numerous countries around the world. Further, the report also provides insights into market developments, trends, supply and demand changes across various regions across the globe. Thereby, the report provides a holistic view on the Genetic Engineering Market in order to help decision makers with various strategic insights and future outlook. The Genetic Engineering market is expected to witness continued growth during the forecast period from 2020 to 2028.

Leading companies reviewed in the Genetic Engineering Market report are: New England Biolabs, Integrated DNA Technologies, Transposagen Biopharmaceuticals, Inc., Amgen Inc., Sangamo Therapeutics, Inc., Genentech, Inc.

Get Free Exclusive Sample of this Premium Report at: https://www.zealinsider.com/report/9610/genetic-engineering-market#sample

The report covers various aspects of the Genetic Engineering market segmented into product type, application and end-use. The report provides market numbers for the years 2018 and 2019 based on actual market findings also market estimates for forecasts for the period from 2020 to 2020 for each of the products types, applications and end-use segments.

Furthermore, the report includes a detailed competitive analysis among the market participants in the Genetic Engineering market. The report offers an in-depth comparative analysis of the competitors in the market based on their product offerings, market share and geographic presence. Some of the leading companies covered in the report include New England Biolabs, Integrated DNA Technologies, Transposagen Biopharmaceuticals, Inc., Amgen Inc., Sangamo Therapeutics, Inc., Genentech, Inc.

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Genetic Engineering Market Segmentation, By Product Type:DNAase, Metazoans, Micrococcal nuclease, Metazoans, RNase A, RNase H, RNase III,, RFLP (Restriction Fragment Length Polymorphism), AFLP (Amplified Fragment Length Polymorphism), SSLP (Simple sequence length polymorphism), Others

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Genetic Engineering Market by Manufacturers, Regions, Type and Application, Forecast To 2026 New England Biolabs, Integrated DNA Technologies,...

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Further guidance required for assessment of gene drive technology, says EFSA – EURACTIV

Posted: November 20, 2020 at 3:57 pm

Existing guidelines are adequate for evaluating risks associated with gene-drive modified insects, but further guidance is needed for some areas, most notably for environmental risk assessments, according to an opinion of the EUs food safety agency (EFSA).

After being mandated by the European Commission, EFSAs experts on genetically modified organisms (GMOs) published the scientific opinion related to engineered gene drives on Thursday (12 November), specifically focusing on gene drive modified disease-transmitting insects, primarily mosquitoes.

The evaluation was requested to explore the issue ahead of the consideration of any possible applications of the technology and is also designed to support the EU in discussions on the biosafety of GMOs in international fora such as the United Nations.

It found that while existing guidelines are sufficient for evaluating risks associated with technology, further guidance is needed for some areas, such as molecular characterisation, environmental risk assessment and post-market environmental monitoring.

Synthetic gene drives are a new form of genetic engineering, created via the genetic engineering method CRISPR/CAS9, and are intended to permanently modify or eradicate populations, or even whole species, in the wild.

The idea of gene drive technology is to force the inheritance of detrimental genetic traits. In this way, scientists hope to reprogramme or eradicate species such as disease-carrying insects and invasive species.

This is a key distinction between gene-drive organisms (GDOs) and genetically modified organisms (GMOs), which are explicitly designed to contain the spread of modified traits.

Scientists say that gene drive technology could play a key role in suppressing or modifying mosquito populations, thus potentially eradicating the life-threatening diseases they carry, such as malaria.

Recently, Imperial College London created a modification that was able to eliminate populations of malaria-carrying mosquitoes in lab experiments, funded by the Bill & Melinda Gates Foundation under the Target Malariaproject.

The technology is also being explored to control agricultural pests, eradicate invasive species, and rescue endangered species, with research rapidly evolving in this area.

After over 78 environmental and agricultural organisations signing a letter this week calling for a moratorium on gene drive technology, EURACTIV took a closer look at the controversial technology to find out about what it is and the implications it holds.

However, the report acknowledges there is concern that this emerging technology may have possible and irreversible side effects.

While Mareike Imken of the German association Save our Seeds welcomed EFSAs conclusion that existing guidelines for genetically engineered insects are insufficient for undertaking environmental risk assessments, she raised concerns that the report failed to acknowledge other key issues.

EFSA does not acknowledge a key challenge for the risk assessment and monitoring of genetically engineered gene drive organisms so-called next-generation effects, she highlighted.

These next-generation effects would encompass unintended changes to the biological characteristics in the offspring of GDOs, which she said would likely happen due to the repeated and uncontrollable process of genetic engineering that gene drives set in motion in nature.

The likely impossibility to model and predict next-generation-effects, as already observed in the offspring of genetically engineered plants, calls for the establishment of cut-off-criteria for risk assessment.

She added that decision-making about this technology needs to be informed by more than risk assessment, stressing that there is an urgent need for a broader political debate and processes for participatory and inclusive societal deliberation around the desirability, costs and benefits of this technology.

[Edited by Zoran Radosavljevic]

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Taking Cultured Meat to the Next Level – Technology Networks

Posted: November 20, 2020 at 3:57 pm

With its origins in the late 1990s, lab-grown or cultured meat, is produced by providing stem cells extracted from the muscle of an animal with a suitable growth medium and nutrients, enabling them to proliferate and then differentiate to form muscle tissue. Creating meat in this way could help to address some of the environmental and ethical issues associated with livestock farming, as well as offer health benefits to consumers.Pairing cellular agriculture with genetic engineering could also enable the development of novel foods, with non-native features, that may be nutritionally enhanced. In a study recently published in Metabolic Engineering, researchers from Tufts University engineered bovine cells to endogenously produce phytoene, lycopene and -carotene, and found a reduction in lipid oxidation levels when this cultured meat was cooked.

Technology Networks had the pleasure of speaking to Andrew Stout, lead author of the study, to learn how these cells were created and explore the benefits of engineering in the abilities to produce additional nutrients. Andrew also discussed some of the challenges that are so far limiting the wider commercialization of cultured meat and how this may change in the future.

Anna MacDonald (AM): Can you give us an overview of the process by which the cow cells were engineered to produce the carotenoids?Andrew Stout (AS): To do this, we inserted three genes into the cells which encode enzymes that convert native compounds into carotenoids. Specifically, the first gene in this pathway (phytoene synthase) takes a native chemical and turns it into the carotenoid phytoene. The second gene (phytoene desaturase) turns some of that phytoene into a second carotenoid called lycopene. And the third gene (lycopene cyclase) turns some of that lycopene into a third carotenoid called beta-carotene. In that way, we're able to get cow cells to produce three different carotenoids that aren't naturally produced in bovine tissue. To engineer the cells, we used a system called the Sleeping beauty transposon system. This system is essentially a "cut and paste" tool which randomly cuts open the cells' genomes and inserts new DNA which we provide (in this case, the genes for carotenoid-producing enzymes).

AM: Why were beta-carotene, phytoene and lycopene chosen in particular?AS: There were several reasons for this. The first and most important was their role as dietary antioxidants. A key mechanistic link between red meat consumption and colorectal cancer is through lipid oxidation. This oxidation leads to the production of free radicals that can interact with tissue in the colon, damage cellular DNA, and ultimately contribute to cancer formation. Antioxidants can act to "quench" those free radicals, thus potentially inhibiting their cancer-causing potential. As carotenoids are powerful antioxidants, they offer a promising target for improving the nutritional features of cell-cultured meat.

Other reasons include the importance of beta-carotene as a vitamin A precursor, previous demonstrations of phytoene synthase efficacy in mammalian cells, and also as a sort of homage to golden rice, the first major demonstration of using genetic engineering to nutritionally enhance a food product.

AM: Were there any side-effects as a result of the nutritional engineering?AS: There were a few. The most obvious was a reduction in growth rate in bovine satellite cells that were engineered with carotenoid-producing enzymes. This would have negative implications for production processes if it proves to be unavoidable. Interestingly, though, in immortalized mouse muscle cells, this reduction in growth rate wasn't seen. Instead, cells producing carotenoids actually grew faster than non-engineered cells. One explanation for this could be that immortalized cells are more "robust" and are more amenable to engineering than the primary (non-immortalized) cow muscle cells we used. It's possible that immortalized cow cells would show growth-effects more like those seen in the mouse cells, which would turn this production down-side into a production up-side. Another side effect we saw was a change in color of the cells -- they took on a reddish tinge with the production of the carotenoids. I don't think this is really a "positive" or "negative" effect, but it is pretty interesting. Other potential side-effects that would need to be looked into would be the effects of carotenoids on cell differentiation, on the prevalence of other nutrients (e.g., cholesterol, etc.), and on flavor, texture, aroma, etc.

Karen Steward (KS): Why do you think you saw lower levels of lipid oxidation when the cell cultured meat was cooked compared to conventional meat?AS: Since carotenoids are antioxidants, they act to quench oxidation in cells during storage, cooking, etc., so we would expect lower lipid oxidation if the cells are producing carotenoids and therefore increasing the total cellular level of antioxidants.

KS: What do you see are the benefits of engineering in the abilities to produce additional phytonutrients to beef cells, as opposed say to having a traditional steak with some vegetables? Is there a risk that in providing these nutrients through meat intake a diet would consequently lack fibre which could impact gut health?AS: This is a fun question! I think we're an extremely long way from actually being able to use this technology to replace vegetables on our plates (and anyways, what a culinarily boring world that would be!) I like to think of this technology not as a replacement of vegetables, but an enhancement of meat. For instance, not all vegetables are high in carotenoids, so if you can get those nutrients from another source in your meal, then your overall consumption of them can increase. Also, the roll of carotenoids in specifically inhibiting oxidation in meat can act to mitigate some of the negative health implications of meat consumption without aiming to reduce vegetable consumption. As a final note, I'd like to think of this work as really just the tip of the iceberg of what's possible. There are so many options for enhancing meat with this or similar technologies--enhanced flavor, therapeutic activity, enhanced smell, etc. I think there's a world of totally novel foods that are possible and that would expand our culinary palette, not reduce it.

KS: Is there any need to start with cow cells? Could you essentially start with any cell type or are there limitations?AS: No need at all! I think this would likely work for all mammalian cells, and there's a strong chance it would work for avian and fish cells as well. We wanted to work with bovine cells because beef is such a major contributor to meat-associated greenhouse gas production and is one of the main red meats consumed around the world. As such, I think it's a really important target for all cultured meat work, including nutritional engineering.

AM: What challenges are so far limiting the wider commercialization of cultured meat?AS: The key hurdles are cost and scale. The field needs to reduce the cost of growth media (likely by reducing the cost of growth factors, reducing cellular reliance on growth factors, finding growth-factor alternatives, or other creative solutions), and to increase the scalability of cell culture (increased growth rate, increased maximum cell density, etc.). There are certainly plenty of other challenges, such as regulatory and consumer reception, demonstration of nutritional and food-quality value, and demonstration of food-safety, but I think that right now cost and scale still reign supreme.

AM: Where do you see the future of cellular agriculture headed?AS: A good question! I'll answer for two slightly different technologies.

First, for cultured meat specifically:

I think in the near future, the field is heading towards a bit of a "realignment" or specification in terms of goals, expectations, hype, etc. I think that this can be seen in some of the ways that companies are starting to look at their products with a bit more nuance, such as looking at the possibility of hybrid cell-based/plant-based products, which could overcome some of the cost/scale barriers of a fully cell-cultured product. Beyond that, I like to think that there will be an expansion of creative solutions to problems, or creative new ways of thinking about cell cultured meat. This could come in the form of looking at agricultural waste products for cell culture components, exploring novel genetic strategies to improve growth / reduce cost, or looking into alternate culture strategies / bioreactors.

Then for cellular agriculture more generally:

I think cellular agriculture in general, while certainly offering its own challenges and hurdles, is a lot further along the developmental pathway than cultured meat. I'm thinking here of products that are already on the market and demonstrably feasible such as recombinant milk proteins (Perfect Day Foods), recombinant collagen proteins (Geltor, Inc.), or recombinant proteins to improve plant-based products (Impossible Foods). I think these technologies are going to continue coming out and coming down in cost, allowing a bunch of new awesome products to come out and accelerate the development of plant-based or fermentation-derived products.

Andrew Stout was speaking to Anna MacDonald and Dr Karen Steward, Science Writers for Technology Networks.

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‘A plague to be reckoned with’: UMN research creates a buzz with invasive fruit fly research – Minnesota Daily

Posted: November 20, 2020 at 3:57 pm

In breeding genetically sterile males, researchers aim to develop a new genetic pesticide.

In the Gortner Laboratory on the St. Paul campus, University of Minnesota graduate student Nate Feltman examines a fruit fly under a microscope. About three millimeters in diameter, the spotted wing drosophila has been wreaking havoc on many soft-skinned berries in almost all of the states in the U.S., including Minnesota.

With a taste for fruits like raspberries, strawberries, blueberries and cherries, the invasive species has hit Minnesota berry growers by storm in the peak of their harvest season since it was first observed in the U.S. in 2008. Laying eggs in ripening fruit, the flies make fruit spoil quicker and make it unmarketable for farmers.

A team of researchers at the University are looking for a way to introduce sterile male spotted wing drosophila flies into the population as a form of genetic pest control, helping farmers in a way that other pesticides and proactive measures have not.

In early November, assistant professor Mike Smanski published an article about a new breakthrough in this research, demonstrating for the first time this kind of genetic engineering was possible in the common fruit fly. This shows that researchers could engineer this work into spotted wing drosophila in the future.

The Universitys Smanski Lab has also studied this technique in mosquitoes, zebra fish and carp, but never with this type of fruit fly, he said.

These are all a new class of genetic pesticide, basically, that allow you to engineer the pest organism itself and convert that pest organism into the pesticide, Smanski said.

Through this work the researchers can create a pest that is biologically the same, but when the females mate with these genetically modified males, they will not produce viable offspring, he said.

This sterile insect technique can be helpful not only in reducing the population of insects, but in reducing the impacts of insecticides on surrounding species and nearby ecosystems, said Feltman, a second-year biochemistry, molecular biology and biophysics graduate student.

As part of the second phase of the research, they will be doing lab tests on the genetically modified spotted wing drosophila, he said. The hope is that the genetic work will prevent the flies from producing offspring.

Over the past decade, researchers have placed traps to study the flies in various farms around the state, including The Berry Patch in Forest Lake, Minnesota.

Kevin Edberg, an owner of the farm, said he first saw the spotted wing drosophila about five or six years ago. His farm is primarily composed of raspberries, strawberries and blueberries that customers pick themselves. Since the flies have come in and made the fruit rot prematurely, he has lost the last week of his harvest season, which is generally one of the most profitable weeks of the year.

Edberg started putting up traps filled with apple cider vinegar to capture the flies and monitor when they come out. In early July, he would catch up to four flies per trap. As the season goes on however, he will catch almost 600 per trap.

Of all the changes that Ive seen, and all of the challenges that have evolved over the last 40 years, [the spotted wing drosophila is] the one that has been the biggest game changer in how we manage and grow, he said.

Traditional avenues of pest management do not work either, he said, which makes it even harder to navigate how to stop them. And if they do not control it one year, they will come back worse the next.

Jerry Untiedt, owner of Untiedts Vegetable Farm Inc. in Waverly, Minnesota, is another berry farmer University researchers have been working with.

Because he uses a high tunnel an unheated greenhouse and sweeps, blows and vacuums the rows between his crops to get rid of rotting fruit that attracts the bugs, Untiedt said he has fared better than other farms in the industry. Anecdotally, Untiedt said that 40% to 50% of raspberry growers no longer grow raspberries because the pest management is too complicated and costly.

He said he is grateful for the Universitys work because without their research, there would not be much known about the spotted wing drosophila.

This is of utmost importance because most people dont understand the biology of this fruit fly and what it could do to this industry, Untiedt said. If youre not vigilant in your management, it can actually destroy your entire crop. Literally, a plague to be reckoned with.

Correction: A previous version of this story misstated the Smanski Labs progress with genetic engineering in some organisms.

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Influence of PSRC1, CELSR2, and SORT1 Gene Polymorphisms on the Variab | PGPM – Dove Medical Press

Posted: November 20, 2020 at 3:57 pm

Laith N AL-Eitan,1 Barakat Z Elsaqa,2 Ayah Y Almasri,1 Hatem A Aman,1 Rame H Khasawneh,3 Mansour A Alghamdi4,5

1Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; 3Department of Hematopathology, King Hussein Medical Center (KHMC), Royal Medical Services (RMS), Amman 11118, Jordan; 4Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabi; 5Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia

Correspondence: Laith N AL-EitanDepartment of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanTel +962-2-7201000 ext 23464Email lneitan@just.edu.jo

Background: Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. Several cardiovascular diseases require therapy with warfarin, an anticoagulant with large interindividual variability resulting in dosing difficulties. The selected genes and their polymorphisms have been implicated in several Genome-Wide Association Study (GWAS) to be associated with cardiovascular disease.Objective: The goal of this study is to discover if there are any associations between rs646776 of PSRC1, rs660240 and rs12740374 of CELSR2, and rs602633 of SORT1 to coronary heart disease (CHD) and warfarin dose variability in patients diagnosed with cardiovascular disease undergoing warfarin therapy.Methods: The study was directed at the Queen Alia Hospital Anticoagulation Clinic in Amman, Jordan. DNA was extracted and genotyped using the Mass ARRAY system, statistical analysis was done using SPSS.Results: The study found several associations between the selected SNPs with warfarin, but none with cardiovascular disease. All 4 studied SNPs were found to be correlated to warfarin sensitivity during the stabilization phase except rs602633 and with warfarin dose variability at the initiation phase. CELSR2 SNPs also showed association with dose variability during the stabilization phase. Also, rs646776 and rs12740374 were linked to warfarin sensitivity over the initiation phase. Only rs602633 was associated with INR treatment outcomes.Conclusion: The findings presented in this study found new pharmacogenomic associations for warfarin, that warrant further research in the field of genotype-guided warfarin dosing.

Keywords: warfarin, SNPs, pharmacogenetics, Jordan

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Gene Therapy Market is Projected to Reach $4,402 million by 2023 | Leading key players are Novartis, Kite Pharma, GlaxoSmithKline , Spark Therapeutics…

Posted: November 20, 2020 at 3:57 pm

The global gene therapy market was valued at $584 million in 2016, and is estimated to reach $4,402 million by 2023, registering a CAGR of 33.3% from 2017 to 2023. Gene therapy is a technique that involves the delivery of nucleic acid polymers into a patients cells as a drug to treat diseases. It fixes a genetic problem at its source. The process involves modifying the protein either to change the genetic expression or to correct a mutation. The emergence of this technology meets the rise in needs for better diagnostics and targeted therapy tools. For instance, genetic engineering can be used to modify physical appearance, metabolism, physical capabilities, and mental abilities such as memory and intelligence. In addition, it is also used for infertility treatment. Gene therapy offers a ray of hope for patients, who either have no treatment options or show no benefits with drugs currently available. The ongoing success has strongly supported upcoming researches and has carved ways for enhancement of gene therapy.

Top Companies Covered in this Report: Novartis, Kite Pharma, Inc., GlaxoSmithKline PLC, Spark Therapeutics Inc., Bluebird bio Inc., Genethon, Transgene SA, Applied Genetic Technologies Corporation, Oxford BioMedica, NewLink Genetics Corp.

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The gene therapy market is a widely expanding field in the pharmaceutical industry with new opportunities. This has piqued the interests of venture capitalists to explore this market and its commercial potential. Major factors that drive the growth of this market include high demands for DNA vaccines to treat genetic diseases, targeted drug delivery, and high incidence of genetic disorders. However, the stringent regulatory approval process for gene therapy and the high costs of gene therapy drugs are expected to hinder the growth of the market.

The global gene therapy market is segmented based on vector type, gene type, application, and geography. Based on vector type, it is categorized into viral vector and non-viral vector. Viral vector is further segmented into retroviruses, lentiviruses, adenoviruses, adeno associated virus, herpes simplex virus, poxvirus, vaccinia virus, and others. Non-viral vector is further categorized into naked/plasmid vectors, gene gun, electroporation, lipofection, and others. Based on gene type, the market is classified into antigen, cytokine, tumor suppressor, suicide, deficiency, growth factors, receptors, and others. Based on application, the market is divided into oncological disorders, rare diseases, cardiovascular diseases, neurological disorders, infectious disease, and other diseases. Based on region, it is analyzed across North America, Europe, Asia-Pacific, and LAMEA.

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Table Of Content

CHAPTER 1: INTRODUCTION

CHAPTER 2: EXECUTIVE SUMMARY

CHAPTER 3: MARKET OVERVIEW

CHAPTER 4: GENE THERAPY MARKET, BY VECTOR TYPE

CHAPTER 5: GENE THERAPY MARKET, BY GENE TYPE

CHAPTER 6: GENE THERAPY MARKET, BY APPLICATION

CHAPTER 7: GENE THERAPY MARKET, BY REGION

CHAPTER 8: COMPANY PROFILE

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Gene Therapy Market is Projected to Reach $4,402 million by 2023 | Leading key players are Novartis, Kite Pharma, GlaxoSmithKline , Spark Therapeutics...

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Solve suffering by blowing up the universe? The dubious philosophy of human extinction – The Conversation UK

Posted: November 20, 2020 at 3:57 pm

At a time when humans are threatening the extinction of so many other species, it might not seem so surprising that some people think that the extinction of our own species would be a good thing. Take, for example, the Voluntary Human Extinction Movement, whose founder believes that our extinction would put an end to the damage we inflict on each other and ecosystems more generally.

Or theres the South African philosopher David Benatar, who argues that bringing people into existence always does them harm. He recommends we cease procreating and gradually desert the Earth.

But humans arent the only beings to feel pain. Non-human animals would continue suffering without us. So, driven by a desire to eliminate suffering entirely, some people have shockingly advocated taking the rest of nature with us. They recommend that we actively abolish the world, rather than simply desert it.

This disturbing and extremist position goes surprisingly far back in history.

Around 1600 years ago, Saint Augustine suggested that humans stop procreating. He endorsed this, however, because he wanted to hasten the Last Judgement and the eternity of joy thereafter.

If you dont believe in an afterlife, this becomes a less attractive option. Youd have to be motivated exclusively by removing suffering from nature, without any promise of gaining supernatural rewards. Probably the first person to advocate human extinction in this way was Arthur Schopenhauer. He did so 200 years ago, in 1819, urging that we spare the coming generations of the burden of existence.

Schopenhauer saw existence as pain so he believed we should stop bringing humans into existence. And he was clear about the result if everyone obeyed: The human race would die out.

But what about the pain of non-human animals? Schopenhauer had an answer, but it wasnt a convincing one. He was a philosophical idealist, believing that the existence of external nature depends on our self-consciousness of it. So, with the abolition of human brains, the sufferings of less self-aware animals would also vanish as they ceased to exist without us around to perceive them.

Even on Schopenhauers own terms, theres a problem. What if other intelligent and self-conscious beings exist? Perhaps on other planets? Surely, then, our sacrifice would mean nothing; existence and painful perception of it would continue. It fell to Schopenhauers disciple, Eduard von Hartmann, to propose a more complete solution.

Hartmann, born in Berlin in 1842, wrote a system of pessimistic philosophy that was almost as lengthy as his impressive beard. Infamous in his own time, but completely forgotten in ours, Hartmann proposed a shockingly radical vision.

Writing in 1869, Hartmann rebuked Schopenhauer for thinking of the problem of suffering in only a local and temporary sense. His predecessors vision of human extinction by sexual continence would not suffice. Hartmann was convinced that, after a few aeons, another self-conscious species would re-evolve on Earth. This would merely perpetuate the misery of existence.

Hartmann also believed that life exists on other planets. Given his belief that most of it was probably unintelligent, the suffering of such beings would be helpless. They wouldnt be able to do anything about it.

So, rather than only destroying our own kind, Hartmann thought that, as intelligent beings, we are obligated to find a way to eliminate suffering, permanently and universally. He believed that it is up to humanity to annihilate the universe: it is our duty, he wrote, to cause the whole kosmos to disappear.

Hartmann hoped that if humanity did not prove up to this task then some planets might evolve beings that would be, long after our own sun is frozen. But he didnt think this meant we could be complacent. He noted the stringency of conditions required for a planet to be habitable (let alone evolve creatures with complex brains), and concluded that the duty might fall exclusively on humans, here and now.

Hartmann was convinced this was the purpose of creation: that our universe exists in order to evolve beings compassionate and clever enough to decide to abolish existence itself. He imagined this final moment as a shockwave of deadly euthanasia rippling outwards from Earth, blotting out the existence of this cosmos until all its world-lenses and nebulae have been abolished.

He remained unclear as to exactly how this goal would be achieved. Speaking vaguely of humanitys increasing global unification and spiritual disillusion, he hinted to future scientific and technological discoveries. He was, thankfully, a metaphysician not a physicist.

Hartmanns philosophy is fascinating. It is also unimaginably wrong. This is because he confuses the eradication of suffering with the eradication of sufferers. Conflating this distinction leads to crazy visions of omnicide. To get rid of suffering you dont need to get rid of sufferers: you could instead try removing the causes of pain. We should eliminate suffering, not the sufferer.

Indeed, so long as there are intelligent beings around, theres at least the opportunity for a radical removal of suffering. Philosophers such as David Pearce even argue that, in the future, technologies like genetic engineering will be able to entirely phase it out, abolishing pain from the Earth. With the right interventions, Pearce contends, humans and non-humans could plausibly be driven by gradients of bliss, not privation and pain.

This wouldnt necessarily need to be a Brave New World, populated by blissed-out, stupefied beings: plausibly, people could still be highly motivated, just by pursuing a range of sublime joys, rather than avoiding negative feeling. Pearce even argues that, in the far future, our descendents might be able to effect the same change on other biospheres, throughout the observable universe.

So, even if you think removing suffering is our absolute priority, there is astronomical value in us sticking around. We may owe it to sufferers generally.

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Avrobio tracks improvements in first patient treated with Gaucher gene therapy – FierceBiotech

Posted: November 19, 2020 at 10:58 am

Avrobio has shared data on the first Gaucher disease patient to receive its gene therapy AVR-RD-02. The patient, who was stable on enzyme replacement therapy at baseline, experienced a 22% drop in a toxic metabolite after receiving AVR-RD-02 and stopping taking the standard of care.

Gaucher, like the Fabry disease targeted by Avrobios lead prospect, is currently treated using enzyme replacement therapies sold by Sanofi and Takeda, which entered the market through its takeover of Shire. However, a significant minority of patients experience physical limitations despite treatment. Negative outcomes include bone pain and spleen enlargement. Johnson & Johnsons Zavesca offers an oral alternative, but there remain unmet medical needs.

Avrobio is developing AVR-RD-02 to address those needs. The data shared as part of Avrobios R&D day mark the start of the effort to show AVR-RD-02 performs as hoped in the clinic.

The first patient to receive AVR-RD-02 discontinued enzyme replacement therapy one month before taking the gene therapy. Three months after receiving the gene therapy, levels of Gaucher biomarker lyso-Gb1 had fallen 22%. The patients level of plasma chitotriosidase, a biomarker of cells associated with severe organ damage, was down 17%. Hemoglobin and platelets were in the normal range.

AVR-RD-02 triggered those changes without causing serious adverse events. The data drop offers an early indication that Avrobio may be able to improve outcomes by harvesting hematopoietic stem cells, adding a gene that encodes for glucocerebrosidase and reinfusing the cells back into the same patient. With enzyme replacement therapies costing healthcare systems up to $400,000 a year per patient, there is scope for AVR-RD-02 to cut the cost of treating Gaucher disease.

Avrobio shared the early look at clinical data on AVR-RD-02 alongside updates about other assets. There is now more than three years of data on some Fabry patients treated with Avrobios lead asset, putting the company in a position to plot a path to accelerated approval. Avrobio plans to submit its briefing book to the FDA by the end of the year to align on an accelerated approval strategy.

The update also covered cystinosis candidate AVR-RD-04. The first patient to receive the candidate is off oral and eye drop cysteamine 12 months after receiving the gene therapy. The number of crystals in the patients skin are down 56%, leading Avrobio to posit they may have gained the ability to make their own functional cystinosin protein.

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