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New clinical trials from University Hospitals Seidman Cancer Center to begin with human protein following successful on-site approach to producing and…

Posted: December 24, 2021 at 2:33 am

CLEVELAND- Newly designed chimeric antigen receptor (CAR) T-cells targeting the CD19 antigen are effective in treating adults and children with B-cell malignancies, especially when produced under place-of-care manufacturing which is available at University Hospitals (UH) Seidman Cancer Center. Thats the conclusion of a recent study published in the prestigious journal Nature Communications, detailing two Phase I clinical trials of CAR19 T-cells used to treat patients with relapsed/refractory pediatric B-cell Acute Lymphocytic Leukemia (ALL) or adult B-cell Lymphoma.

Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralized facilities, says study co-author Jane Reese Koc, Cellular Therapy Operations Director at UH Seidman Cancer Center and the National Center for Regenerative Medicine at Case Western Reserve University. The Cellular Therapy Lab is shared by the National Center for Regenerative Medicine, Case Comprehensive Cancer Center and UH Seidman Cancer Center. The results of this study support the safety and efficacy of this approach.

One of the major advantages of this approach is the ability to treat patients significantly quicker than is feasible with commercial CAR T products, adds study co-author David Wald, MD, PhD, Associate Director for Basic Research at the Wesley Center for Immunotherapy at UH Seidman Cancer Center and Associate Professor of Pathology Case Western Reserve University School of Medicine. Commercial products can take three to six weeks to be manufactured. The time savings to treatment with the method is important for these patients that have advanced malignancies. We are working with partners to develop even more rapid methods to shorten the manufacturing method down to a single day.

The Phase I trials involved 31 pediatric and 23 adult patients, located in both Russia and Cleveland. After a median follow-up of 17 months, one-year survival rate of ALL complete responders was 79.2% and median duration of response is 10.2 months. For non-Hodgkin lymphoma (NHL), complete responders one-year survival was 92.9%, and median duration of response has not been reached. The CAR19 T-cells were first tested in cancer cell lines and mouse xenograft models, with positive results.

For NHL, the results were excellent, says hematologist Leland Metheny, MD, who is also involved in these clinical trials at UH Seidman Cancer Center. The results showed they were curative for a significant portion.

Importantly, in the mouse xenograft experiments, fresh CAR19 T-cells produced in the local facility were shown to provide an advantage over cryopreserved cells more commonly used in CAR T applications. Administration of fresh CAR19 T-cells yielded significantly lower tumor burden as compared to dose-matched frozen CAR19 T-cells on study days 11 and 13. On study days 21 and 28, tumors were similarly and potently rejected by both fresh and frozen cell-treated groups. However, fresh cells reduced the tumor burden sooner by eight days, and immediately started reducing the tumor burden, while frozen CAR19 T-cells first permitted tumor growth before controlling growth.

The cells that were given fresh acted much better and more effective in mice in getting rid of the NHL than the frozen cells, Dr. Metheny says. There is something we dont know yet about the impact of the freezing technique that is impacting the CAR T-cells.

In addition to these two clinical trials, Dr. Methenys colleagues at UH Seidman Cancer Center are also conducting a CAR T trial that uses fully human protein one just a handful of sites nationwide to offer this option to patients.

The antibody part of the antigen receptor that were putting on the surface of the T cell is a fully human sequence, says UH Seidman oncologist Benjamin Tomlinson, MD, who is leading this trial. In theory, it may have fewer adverse events, so be slightly safer, while still attacking the same target. The biggest question is whether by not having a foreign component, it may be a little bit more effective in instigations in the signaling. Human to human should connect a little bit better than human to mouse, and it may not generate the type of reactions that we are used to seeing with a regular CAR Ts. So that's what we're exploring. We have opened this humanized CAR T trial and have treated patients with lymphoma and ALL successfully.

In addition, Dr. Wald and colleagues recently reported at the American Society of Hematology meeting on their work identifying potential biomarkers that may help predict outcomes of the patients receiving CAR T-cell therapy.

We hope this will help to design next generation CAR T-cell therapies, he says.

###

About University Hospitals Seidman Cancer Center

UH Seidman Cancer Center is the only freestanding cancer hospital in Northeast Ohio, where all clinicians and staff are dedicated to the prevention, diagnosis and treatment of cancer while researching new and innovative treatment options through clinical trials. Nationally ranked cancer care is also available to patients through the 11-county region at 18 community-based locations. Our UH Seidman specialists make up 14 cancer-specific teams focused on determining integrated care plans tailored to patients needs. UH Seidman Cancer Center is part of the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center at Case Western Reserve University, one of 51 comprehensive cancer centers in the country. Patients have access to advanced treatment options, ranging from a pioneering stem cell transplant program founded more than 40 years ago and a wide range of immunotherapy to the first and only proton therapy center in northern Ohio for adults and children. Go to UHhospitals.org/Seidman for more information.

About University Hospitals / Cleveland, OhioFounded in 1866, University Hospitals serves the needs of patients through an integrated network of 23 hospitals (including 5 joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio.The systems flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Oxford University and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top childrens hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including Americas Best Hospitals from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH isone of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visitUHhospitals.org.

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Osmolarity – an overview | ScienceDirect Topics

Posted: December 24, 2021 at 2:32 am

3 The HOG Signaling System

The HOG pathway (Fig. 2.1) is one of the best understood and most intensively studied MAPK systems. First, components (Hog1 and Pbs2) were identified in a genetic screen for osmosensitive mutants deficient in glycerol accumulation (Brewster et al., 1993). In parallel, inactivation of SLN1, encoding the single yeast sensor histidine kinase, was found to be lethal (Ota and Varshavsky, 1993). This lethality, which was later shown to be because of inappropriate overactivation of the Hog1 kinase, was suppressed by knockout of any of the genes SSK1, SSK2, PBS2, and HOG1, thereby defining a linear pathway from Sln1 to Hog1. In addition, overexpression of PTC1, PTP2, or PTP3 suppressed lethality of the sln1 mutant, defining those as negative elements of the pathway (Maeda et al., 1994; Posas and Saito, 1997; Posas et al., 1996). Finally, the observation that ssk1 as well as ssk2 ssk22 mutants were osmotolerant while deletion of PBS2 and HOG1 caused osmosensitivity prompted genetic screens employing synthetic enhancement that identified SHO1, STE20, and STE11 as encoding components of the Sho1 branch (Maeda et al., 1995). Identification of the pathway components and characterization of their order of function represent textbook examples of the power of both targeted and global yeast genetics approaches. In fact, forward genetics, suppressor mutation, multicopy suppression, synthetic enhancement, epistasis analysis, and yeast two hybrid screens were all employed in this context. Particular powerful genetic tools are mutations that activate signaling constitutively. Significant knowledge has emerged on the flow of information through the pathway and hence the mechanisms of signal transduction by combining the genetic tools with in vitro and in vivo protein interaction assays, as well as in vitro protein kinase assays (de Nadal et al., 2002; Hohmann, 2002; O'Rourke et al., 2002; Saito and Tatebayashi, 2004; Tatebayashi et al., 2006).

The HOG signaling system consists of two branches that converge on the MAPKK Pbs2, the Sln1, and the Sho1. Components of the Sho1 branch also take part in pseudohyphal development and mating in S. cerevisiae (O'Rourke and Herskowitz, 1998). In many fungi, it appears that the Sho1 module is not connected to Pbs2 and hence is not involved in osmotic responses (Furukawa et al., 2005; Krantz et al., 2006). This indicates that the Sho1 module might not primarily have a role in osmosensing but rather perceives signals related to cell shape and/or cell surface conditions, in accordance with the role in activation played by the cell polarity machinery. Sho1 is specifically located at sites of cell growth and does not appear to sense turgor changes (Reiser et al., 2000, 2003).

The Sho1 branch consists almost exclusively of proteins shared with the pseudohyphal development pathway and the pheromone response pathway. Signaling specificity seems to be assured by recruitment to scaffold proteins (Sho1, Opy2, Pbs2) and requires the Hog1 kinase. In hog1 mutants, exposure to osmotic stress causes activation of the pseudohyphal and pheromone response pathways and morphological aberrations (Davenport et al., 1999; O'Rourke and Herskowitz, 1998; Rep et al., 2000). The mechanism by which Hog1 prevents such cross talk has not yet been elucidated. Mechanisms involved in activation of the Sho1 branch following osmotic shock have been described in detail using constitutively active Stell and Sho1 mutants as well as protein interaction studies (Tatebayashi et al., 2006). As indicated earlier, the sensing mechanism of osmotic changes in the Sho1 branch is not understood at this point but must be closely related to Sho1 (Tatebayashi et al., 2006). The observation that Sho1 can be replaced by engineered proteins that recruit Pbs2 to the plasma membrane suggests that Sho1 does not function as a sensor itself (Raitt et al., 2000). Sho1 shows much less variation in size than in primary sequence (Krantz and Hohmann, 2006), indicating a structural rather than an enzymatic function.

Sln1 is a sensor histidine kinase related to bacterial twocomponent systems. Such proteins are widespread in fungi and plants (Catlett et al., 2003). Sln1 has a similar domain organization as the bacterial osmosensing histidine kinase EnvZ. Both proteins have two transmembrane domains at their N terminus, which are connected by a large extracellular loop, about 300 amino acids in yeasts. It is believed that the extracellular loop and the transmembrane domains sense turgor changes (Reiser et al., 2003), perhaps by responding to movements of the plasma membrane relative to the cell wall. The homodimer is likely regulated by a structural change, which is propagated from the extracellular sensing domain to the intracellular histidine kinase domain of Sln1 (Posas et al., 1996; Reiser et al., 2003). In S. cerevisiae the Sln1 histidine kinase is a negative regulator of the downstream MAPK cascade; deletion of SLN1 or inactivation of the kinase results in lethal Hog1 overactivation (Maeda et al., 1994). When active (i.e., under ambient conditions), the Sln1 histidine kinase crossphosphorylates within a dimer (Posas et al., 1996), and the phosphate group is transferred via the Sln1 receiver and response regulator domains as well as the Ypd1 phosphotransfer protein to the Ssk1 response regulator protein. Hyperosmotic shock causes inactivation of Sln1 kinase activity and dephosphorylation of Ssk1. This scenario is well supported by mutational analysis of all steps in the phosphorelay system (Posas et al., 1996). Unphosphorylated Ssk1 mediates activation of the redundant MAPKKKs Ssk2 and Ssk22, which in turn activate Pbs2.

The activity and the relative contribution of the two pathway branches to Hog1 kinase activity are usually measured in mutants that are blocked in either branch (Maeda et al., 1995; O'Rourke and Herskowitz, 2004). Whether such experiments reflect activity of the two branches in wildtype cells is presently unknown. It appears that the Sho1 branch has a higher stress threshold for activation (Maeda et al., 1995; O'Rourke and Herskowitz, 2004) and that it is insufficient to mediate maximal pathway activation alone (unpublished data).

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Genetic Engineering – Courses, Subjects, Eligibility …

Posted: December 24, 2021 at 2:31 am

Genetic Engineering is a technology that alters the genetic structure of an organism either by removing or adding DNA.Genetic Engineering, also called genetic modification or genetic manipulation controls the living being's genes using biotechnology. It is an arrangement of innovations used to change the hereditary forms of cells, including the exchange of qualities inside and across species limits to create enhanced or novel living beings. Genetic engineering could potentially fix severegenetic disorders in humans by replacing the defective gene with a functioning one.

Genetic Engineering has been connected in various fields of research, medicine, industrial biotechnology, and agriculture. In research, GMOs are utilized to contemplate quality capacity and articulation through loss of function, gain of function, tracking and expression experiments. By thumping out genes responsible for specific conditions it is possible to create animal model organisms of human diseases. And in addition to producing hormones, immunizations and different drugs genetic engineering can fix hereditary diseases through quality treatment. Similar strategies that are utilized to create medications can likewise have mechanical applications, for example, producing enzymes for detergents, cheeses, and different products.

Genetic engineering as a course is studied at the graduate, postgraduate and doctoral levels. Genetic Engineering is rather a new field of science but with the recent advancement in Biotechnology and the interest of scientists in this particular field, the course in Genetic Engineering is present in almost every major science university. The B.Sc in Genetics or B.Tech in Genetic Engineering course deals with multiple types of problems related to the medical field like the human genome and agriculture. Several institutes also offer Genetic Engineering as an elective course of study in B.Tech Biotechnology programs.

Delhi Technological University, Delhi

Aryabhatta Knowledge University, Patna

SRM University, Chennai

Bharat University, Chennai

Indian Institute of Science, Bangalore

Sharda University, Greater Noida

India has some of the very prestigious institutes engaged in research in the field of Genetics. Candidates can pursue research in these institutes in Genetic Engineering and its various sub-fields.

Genetic engineering is the study of genes and the science of heredity. Genetic engineers or geneticists study living organisms ranging from human beings to crops and even bacteria. These professionals also conduct researches which is a major part of their work profile. The experiments are conducted to determine the origin and governing laws of a particular inherited trait. These traits include medical conditions, diseases, etc. The study is further used to seek our determinants responsible for the inherited trait.

Genetic engineers or Geneticists keep on finding ways to enhance their work profile depending on the place and organization they are working with. In manufacturing, these professionals will develop new pharmaceutical or agricultural products while in a medical setting, they advise patients on the diagnosed medical conditions that are inherited and also treat patients on the same.

Skill sets for Genetic engineers or Geneticists

Strong understanding of scientific methods and rules

complex problem solving and critical thinking

ability to use computer-aided design (CAD)

graphics or photo imaging

PERL, Python

word processing software programs

excellent mathematical, deductive and inductive reasoning, reading, writing, and oral comprehension skills

ability to use lasers spectrometers, light scattering equipment, binocular light compound microscopes, benchtop centrifuges, or similar laboratory equipment

Typical responsibilities of a Genetic Engineering or Geneticist includes:

When a genetic engineer gains a year of experience, one of the regions they can indulge in is hereditary advising, which includes offering data, support, and counsel on hereditary conditions to your patients.

An individual aspiring to pursue a professional degree in Genetic Engineering can begin the B.Sc in Genetics or B.Tech course after his/her 10+2 Science with Physics, Chemistry, Maths, and Biology.

Admission to BTech in Genetic Engineering is made through entrance tests conducted by various universities or through the scores of national engineering entrance examinations like JEE for IITs/NITs & CFTIs across the country.

Genetic Engineering professionals require a bachelors or masters degree in Genetic Engineering or Genetic Sciences for entry-level careers. In any case, a doctoral qualification is required for those looking for free research professions. Important fields of study in Genetic Engineering incorporate natural chemistry, biophysics, or related fields.

Genetic Engineers require a solid comprehension of logical techniques and guidelines, and in addition complex critical thinking and basic reasoning aptitudes. Phenomenal scientific, deductive, and inductive thinking aptitudes, and in addition perusing, composing, and oral cognizance abilities are additionally expected to work in this field.

A semester-wise breakup of the B.Tech Genetic Engineering course is tabulated below

SEMESTER I

SEMESTER II

Mathematics 1

Mathematics 2

English

Material Science

Physics

Principles of Environmental Science

Chemistry

Biochemistry

Basic Engineering 1

Basic Engineering 2

-

Cell Biology

-

Value Education

SEMESTER III

SEMESTER IV

Enzyme Technology

Basic Molecular Techniques

Genetics & Cytogenetics

Molecular Biology

Immunology

Stoichiometry and Engineering Thermodynamics

Microbiology

Bio-press Principles

Mechanical Operations & heat Transfer

Biostatistics

German Language Phase 1/French Language Phase 1/Japanese Language Phase 1

German Language Phase 2/Japanese Language Phase 2/French Language Phase 2

-

SEMESTER V

SEMESTER VI

Advanced Molecular Techniques

Recombinant DNA Technology

Functional Genomics and Microarray Technology

Bioinformatics

Momentum Transfer

Chemical Reaction Engineering

Bioprocess Engineering

Gene Therapy

Biophysics

Biosensors and Biochips

Plant Tissue Culture and Transgenic Technology

-

Personality Development

-

SEMESTER VII

SEMESTER VIII

Bio-separation Technology

Project Work

Animal Cell Culture and Transgenic Technology

Bio-Safety, Bio-ethics, IPR & Patients

Nano-biotechnology in Healthcare

-

Stem Cell Biology

-

Aspirants who wish to join the engineering industry as genetic engineers can apply for the following jobs profiles available:

JOB PROFILE

JOB DESCRIPTION

Genetic Engineer

They apply their knowledge of engineering, biology, and biomechanical principles to the design, development, and evaluation of biological and health systems and products, such as artificial organs, prostheses, instrumentation, medical information systems, and health care and management.

Lecturer/Professor

They teach at the undergraduate and graduate levels in areas allocated and reviewed from time to time by the Head of Department.

Research Scientist

They are responsible for designing, undertaking, and analyzing information from controlled laboratory-based investigations, experiments and trials.

Scientific/Medical Writer

The research, prepare and coordinate scientific publications. The medical writer is responsible for researching, writing, and editing clinical/statistical reports and study protocols, and summarizing data from clinical studies.

Most of the engineering educational institutes shortlist candidates for admission into the BTech in Genetic Engineering course based on engineering entrance exams. These entrance exams are either conducted at the national level like JEE or held in-house by various engineering institutes in the country. Some of the popular engineering entrance examinations aspirants should consider appearing for admissions to UG and PG level Automobile engineering courses are:

Genetic Engineering is particularly the newly evolving field of science with enormous job opportunities. India has become a global hub of research in genetic engineering owing to its vast prospect of treating diseases of genetic disorders. Genetic engineering professionals can work in the filed of medicine, research, industry, and agriculture. Fresh graduates working as research associates can earn anything between INR 3-5 lakh per annum while the salary of scientists generally lies in the range of 9-15 lakh per annum.

India is home to some of the best companies working in the field of Genetic Engineering. Below is provided a list of some of the companies with which candidates can work in the field of research.

Q. Which college is best for genetic engineering?

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Human genetic enhancement – Wikipedia

Posted: December 24, 2021 at 2:31 am

Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases (gene therapy), prevent the possibility of getting a particular disease[1] (similarly to vaccines), to improve athlete performance in sporting events (gene doping), or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence.These genetic enhancements may or may not be done in such a way that the change is heritable (which has raised concerns within the scientific community).[2]

Genetic modification in order to cure genetic diseases is referred to as gene therapy. Many such gene therapies are available, made it through all phases of clinical research and are approved by the FDA. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.[3] As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

Some people are immunocompromised and their bodies are hence much less capable of fending off and defeating diseases (i.e. influenza, ...). In some cases this is due to genetic flaws[clarification needed] or even genetic diseases such as SCID. Some gene therapies have already been developed or are being developed to correct these genetic flaws/diseases, hereby making these people less susceptible to catching additional diseases (i.e. influenza, ...).[4]

In November 2018, Lulu and Nana were created.[5] By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called CCR5 in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus.

Athletes might adopt gene therapy technologies to improve their performance.[6] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[7]

Other hypothetical gene therapies could include changes to physical appearance, metabolism, mental faculties such as memory and intelligence.

Some congenital disorders (such as those affecting the muscoskeletal system) may affect physical appearance, and in some cases may also cause physical discomfort. Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these diseases) may prevent this.

Also changes in the mystatin gene[8] may alter appearance.

Behavior may also be modified by genetic intervention.[9] Some people may be aggressive, selfish, ... and may not be able to function well in society.[clarification needed] There is currently research ongoing on genes that are or may be (in part) responsible for selfishness (i.e. ruthlessness gene, aggression (i.e. warrior gene), altruism (i.e. OXTR, CD38, COMT, DRD4, DRD5, IGF2, GABRB2[10])

There is some research going on on the hypothetical treatment of psychiatric disorders by means of gene therapy. It is assumed that, with gene-transfer techniques, it is possible (in experimental settings using animal models) to alter CNS gene expression and thereby the intrinsic generation of molecules involved in neural plasticity and neural regeneration, and thereby modifying ultimately behaviour.[11]

In recent years, it was possible to modify ethanol intake in animal models. Specifically, this was done by targeting the expression of the aldehyde dehydrogenase gene (ALDH2), lead to a significantly altered alcohol-drinking behaviour.[12] Reduction of p11, a serotonin receptor binding protein, in the nucleus accumbens led to depression-like behaviour in rodents, while restoration of the p11 gene expression in this anatomical area reversed this behaviour.[13]

Recently, it was also shown that the gene transfer of CBP (CREB (c-AMP response element binding protein) binding protein) improves cognitive deficits in an animal model of Alzheimers dementia via increasing the expression of BDNF (brain-derived neurotrophic factor).[14] The same authors were also able to show in this study that accumulation of amyloid- (A) interfered with CREB activity which is physiologically involved in memory formation.

In another study, it was shown that A deposition and plaque formation can be reduced by sustained expression of the neprilysin (an endopeptidase) gene which also led to improvements on the behavioural (i.e. cognitive) level.[15]

Similarly, the intracerebral gene transfer of ECE (endothelin-converting enzyme) via a virus vector stereotactically injected in the right anterior cortex and hippocampus, has also shown to reduce A deposits in a transgenic mouse model of Alzeimers dementia.[16]

There is also research going on on genoeconomics, a protoscience that is based on the idea that a person's financial behavior could be traced to their DNA and that genes are related to economic behavior. As of 2015, the results have been inconclusive. Some minor correlations have been identified.[17][18]

George Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against Alzheimer's disease, disease resistances, higher lean muscle mass and enhanced learning abilities along with some of the associated studies and potential negative effects.[19][20]

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Editing the produce gene – Produce Blue Book

Posted: December 24, 2021 at 2:31 am

I spent part of my workday on Wednesday watching a rerun. It was of a Virtual Town Hall meeting entitled Gene Editing: The Future of the Produce Industry?, by the Produce Marketing Association BB #:153708, originally broadcast July 28.

PMA broadcast it again because of its popularity.

It answered one of the proverbial dumb questions that journalists, if no one else, should ask. In this case, whats the difference between genetic engineering and gene editing?

A rigorous answer to this question would depend on your location because various nations define (and regulate) the two differently.

This is essentially the difference: if an organism has been modified by the insertion of foreign DNA, its genetically modified (a GMO, for short).

Gene editing, on the other hand, is modifying genes in a way that could be achieved by plant breeding, except gene editing takes much less time. (For details, see here).

The United States regulates the two methods differently.

USDA issued this statement in March 2018: USDA does not regulate or have any plans to regulate plants that could otherwise have been developed through traditional breeding techniques as long as they are not plant pests or developed using plant pests. This includes a set of new techniques that are increasingly being used by plant breeders to produce new plant varieties that are indistinguishable from those developed through traditional breeding methods.

As an example of gene editing, panelist Haven Baker, cofounder and chief business officer of Pairwise, points to one of his companys current projects: the pitless cherry.

With conventional breeding, it would take 150 years, he remarks. But his company is three years into the project. He predicts that pitless cherries will be on the market by the end of the decade.

Seedless blackberries are further along: Baker estimates they will be available in a couple of years.

Another item: a watermelon that produces a natural zero-calorie sweetener, which panelist Fayaz Khazi, CEO of Bio Life Systems, says is producing to scale now.

Gene editing, panelist Gilad Gershon, CEO of Tropic Biosciences, says, is very specific. You maybe only change one nutrient, or disease resistance.

One example is TR4 Fusarium wilt, which afflicts Cavendish bananas and, if not checked, can destroy the world banana industry as it is now known.

We try to identify genes that affect Fusarium resistance, and try to fit them to consumer needs, Khazi says.

The panel kept returning to one major theme: the importance of consumer wants in gene editing crops. We try not to guess what the market needs, stresses Khazi.

Indeed, the disconnect between real and perceived consumer needs is the biggest bottleneck, Khazi adds. Surprisingly, the biology of the plant is never the bottleneck.

Currently, no produce items are on the market in this country that are products of gene editing, the panelists noted, although Japan has introduced a tomato with a high GABA content that is available there.

Eventually, Khazi predicts, the two categories of GMO and gene editing will merge.

In any case, gene editing is part of the produce industrys present and will become an increasingly important element of its future. Think of it as plant breeding on fast forward.

And never forget to ask dumb questions.

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Scientists Used CRISPR Gene Editing to Choose the Sex of Mouse Pups – Singularity Hub

Posted: December 24, 2021 at 2:31 am

Do you want a boy or a girl? can be an awkward question.

But in certain circles, its a question thats asked every day. Take agriculture. In a perfect world, most cows would only birth females. Chicks would grow up to be all hens. Sexing a farm animal when theyre at a young age wouldnt be a thingespecially when it means male animals, without the ability to produce milk or eggs, are often culled at a young age to preserve resources.

There might be a better way. This month, a team tapped into the power of CRISPR to control the sex of the offspring in mice. By splicing CRISPR components into the parents genome, the team was able to flip onor offa switch that nearly perfectly determined the sex of their litters.

Unlike previous attempts, the baby mice could go on to have litters of their own of both sexes. The targeted gene used for the edit is conserved across evolution, suggesting the technique could work in more animals than just mice.

But its controversial. Essentially, the technique selectively kills off embryos of a certain sex, which immediately raises ethical red flags. For now, scientists arent concerned about the technology being used in humans due to its complexity. But the study is the latest to showcase biotechs increasing ability to manipulate reproduction.

Its an impressive result and a state-of-the-art solution to producing single-sex species, said Dr. Ehud Qimron at Tel Aviv University, who was not involved in the work.

Skewing the sex of offspring is nothing new. For over a decade, scientists have gradually hijacked the mosquito genome with gene drives to rewrite evolution. The idea is that the genetic edit would override natural selection, spreading across subsequent generations into a dominant gene. Instead of a genes usual 50-50 chance of inheritance, artificial gene drives have a far higher chance of infiltrating the next generation, fundamentally changing a species genetic code. When its a gene that biases the sex of their offspring, a species could gradually only have one sex, leading to their extinction.

Its a doomsday plan with potentially massive benefits, such as curbing malaria. Because female mosquitoes are generally the carrier for the disease, a gene drive that leads to only males is a sure-fire way to reduce transmission. In one study, within a dozen generations, the genetic edit was sufficient to collapse a whole colony of mosquitoes in the lab. Similar studies have been tried in mice.

Its not a perfect solution. The gene edit is powerfulmaybe too much so. With farm animals, the goal isnt to eradicate a species, but rather to bias the sex of the animal towards one side and increase animal welfare. Animal and animal products are used globally, and ethical discussions regarding animal usage are ongoing, said the authors. Over 100,000 male calves are culled each year, and stats for other common farm animals paint a similarly uncomfortable picture.

The new study took a different approach. With CRISPR, the team skewed the sex of only the next generation in mice, allowing the same-sex litters to eventually reproduce normally.

CRISPR has two parts: an RNA guide (the bloodhound that sniffs out the target gene) and Cas9 (a scissor protein that physically cuts the gene). Usually, the two components are encoded into a single carrier, dubbed a vector, and inserted into a cell or animal. By targeting a gene that is essential for reproduction, for example, its then possible to trigger spontaneous failed pregnancies in animals.

But how does that help with sex selection? Let me explain.

The first step was to find a gene critical for embryo survivalone that when disrupted causes synthetic lethality. The team honed in on Top1, well known for its role in DNA repair. Cutting the gene triggers embryos to fail at a very early stage, when theyre just 8 to 16 cells, not yet implanted into the uterine wall and far from viable.

The team then engineered a CRISPR system that targets the start codons of Top1a chunk of DNA that acts as an on switch to activate the gene. Heres the clever part. They split the two components of CRISPR into two vectors.

One part, which carries the genetic code for a guide RNA that targets Top1, was then inserted into a female mouses X chromosome. The other vector, carrying the code for Cas9 scissors, was edited into the males Y chromosome.

When combined, the two components meet up like peanut butter and jelly, forming the full recipe to disrupt Top1. This can only happen in X/Y embryosthose that define maleand so selectively interrupt these embryos from developing. X/X, or genetically female embryos, are spared, as they only contain half of the CRISPR mechanism. The system is flexible. If Cas9 scissors were attached to the males X chromosome, all X/X embryos were eliminated before they grew to 16 cells.

The efficiency of the edit was crazy at 100 percent. Mice born from these genetically-edited parents were completely normal, with a hefty body size and in larger numbers than normally expected, suggesting the edit may cause less stress on the mother. Unlike those born using gene drives, the mice grew up to have perfectly normal litters with both male and female offspring.

The results are a long time in the making. Back in 2019, a team led by Dr. Udi Qimron at Tel Aviv University used CRISPR to produce mice in which 80 percent of the offspring were females. With the new study, the efficacy leaps to 100 percent, with the choice towards either sex. If further tested in farm animals, the technique could be a boost to both animal welfare and conservation.

Its not an entirely comfortable solution for some. To Sue Leary, president of the non-profit Alternatives Research & Development Foundation, You cant solve an ethical problem with another ethical problem, which is genetic engineering. And given the animosity towards GMOs, the new technology, regardless of efficacy, may be dead in the water.

For now, the CRISPR edits arent feasible in humans due to their complexity. Whats clear, though, is that weve begun parsing the biological machinery behind gender selection. Add in recent work on genetically-engineered embryos, or eggs and sperm from stem cells, and were on the fast track for CRISPR to completely change our current conception of reproduction.

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2021: when the link between the climate and biodiversity crises became clear – The Guardian

Posted: December 24, 2021 at 2:31 am

Bats sweltering in their boxes, polar bears and narwhals using up to four times as much energy to survive, birds starving as Turkeys lakes dry up, and unique island species at high risk of extinction as the planet warms. If there was ever any doubt about the inextricable link between the climate emergency and the biodiversity crisis, those doubts were well and truly dispelled in 2021.

The science is clear: climate, biodiversity and human health are fully interdependent, Frans Timmermans, the European Commission vice-president who heads the European Green Deal; Achim Steiner, of the UN Development Programme; and Sandrine Dixson-Declve, of the Club of Rome, wrote before the Cop26 climate conference.

While the much-anticipated Cop15 Kunming biodiversity conference was delayed yet again, Cop26 brought together leaders from across the globe to discuss the climate emergency. Although the pledges on emissions cuts fell short of those required to limit the increase in temperatures to 1.5C, there were promises to halt and reverse global deforestation over the next decade.

Meanwhile, dozens of countries have committed to protecting 30% of the planets land and oceans by 2030, and in September, nine philanthropic foundations pledged $5bn (3.75bn) to finance the 30x30 pledge.

Despite the coronavirus pandemic and the many lockdowns, 2021 saw the worlds scientists, volunteers and conservationists continuing their efforts to protect nature. The International Union for Conservation of Nature launched its new green list of protected and conserved areas, researchers at the Natural History Museum worked on digitising its vast collection, Kenya held its first animal census, and a multimillion-pound project was launched that aims to describe and identify the web of life in large freshwater ecosystems with game-changing DNA technology.

In September, the IUCN world conservation congress in Marseille brought together innovators and policymakers from across the world for talks and debates on subjects as diverse as the universal declaration of the rights of the river, alien species, human-wildlife conflict, the use of smart technology in conservation, genetic engineering and much more.

Not all conservation efforts are down to scientists and policymakers though. There is growing recognition of the vital role communities and indigenous people play in conserving biodiversity and building livelihoods and this year we highlighted projects that included a shade-grown coffee initiative in Peru, islanders rallying to save the coco de mer nut in Seychelles and an army of nature recorders and seed conservers in the UK.

There was good news elsewhere. The flatpack homes for animals that fall victim to wildfires that we highlighted in April have since been trialled in Sydney, where a housing estate of the biodegradable cardboard pods has been put up to give shelter to wildlife after the bushfires.

In response to our piece on conservationists criticising Marks & Spencer for releasing 30 million honeybees, the British retailer filled 500 stores with little signs telling shoppers about the importance of native bumblebees in producing a number of foods. M&S has been really open to learning, said Gill Perkins, chief executive of the Bumblebee Conservation Trust, who believes it is the first UK supermarket to introduce bumblebee labels highlighting the work of these pollinators. She hopes others will follow suit.

Andrew Kerr, who spoke to the Guardian about wanting to create a UK eel rewilding programme, is having discussions with the relevant government ministry in January about the feasibility of getting rewilding permits sorted for this coming eel season.

Since we reported on the proposals to extend Barcelona airport, threatening neighbouring wetlands and a wealth of biodiversity, the plans have been put on hold. The future of the red wolf in North Carolina still hangs in the balance but the US Fish and Wildlife Service says it is planning to release nine wolves from captivity this winter. And an experimental feeding programme has been approved for Floridas manatees, after a record year of deaths.

Over the coming weeks, we will follow up on some of the stories that we covered during 2021 in more depth, but in the meantime, you might like to take a look at some of our favourite articles from the year that celebrate the planets beautiful and intricate biodiversity: why we need to stop treating soil like dirt; the wonderful world of fungi; the value of dead wood; how a wild night out could help you reconnect with nature; and, lastly, a lesson in why some things are worth waiting for, especially when they turn out like this

Find more age of extinction coverage here, and follow biodiversity reporters Phoebe Weston and Patrick Greenfield on Twitter for all the latest news and features

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Opinion: Allow Golden Rice to save lives – pnas.org

Posted: December 24, 2021 at 2:31 am

Vitamin A deficiency (VAD) has killed millions of children in less-developed countries for at least the last three decadesroughly 2 million annually in the early 1990s alone (14). Although the number is declining, it was estimated to be 266,200 (4) at the start of the millennium.

Widespread consumption of the genetically modified rice variety known as Golden Rice offers a potent and cost-effective strategy to combat vitamin A deficiency. Image credit: International Rice Research Institute; photo licensed under CC BY 2.0.

The consumption of the genetically modified rice variety known as Golden Rice (GR) offers a potent and cost-effective strategy to combat VAD. But this innovation has been cast aside owing to fear or false accusations, resulting in numerous lives needlessly lost (13). With the recent exception of the Philippines, governments have not approved the cultivation of GR (5). We believe it should be broadly approved and given the opportunity to save and improve lives.

In high-income nations where populations have access to a diversity of foods, VAD is rare. In many low-income nations, however, populations have limited access to foods rich in vitamin A or beta-carotene, a vitamin A precursor; hence, VAD rates can be dangerously high in children. There have been recent improvements: from 1991 to 2013, the VAD rate among children in low- and middle-income countries declined from 39% to 29%, with notable improvements among children in East and Southeast Asia (4). However, children in sub-Saharan Africa and South and Southeast Asia continue to disproportionately experience VAD and its associated risks: infectious and diarrheal diseases, irreversible blindness and other sensory losses, and premature death (1, 4, 6).

VAD has not been eradicated despite a variety of strategies used globally, including education on the value of dietary diversity, promotion of home gardens and maternal breastfeeding of infants, and community health programs including vitamin A supplementation with syrups or capsules (7). Principally, VAD is caused by insufficient dietary diversity, a result of poverty and agronomic and market constraints. Animal source foods and many kinds of produce are unavailable or expensive in local markets. Conversely, white rice or other cereal grains are easily available and inexpensive but primarily contain carbohydrates while lacking sufficient micronutrient levels.

GR, developed first in the 1990s and then modified in 2004 with transgenes from maize and a common soil bacterium Erwinia uredovora, could be an important public health intervention for VAD populations worldwide. This transgenic, or genetically modified, rice produces beta-carotene, a precursor to vitamin A, in the normally white endosperm (8) and has proven an effective source of vitamin A in humans (9). GR* is now awaiting final approval in Bangladesh. In July 2021, it was approved for cultivation in the Philippines. Other countries will likely follow.

A recent study has estimated that substituting GR for conventional rice could provide 89% to 113% and 57% to 99% of the recommended vitamin A requirement for preschool children in Bangladesh and the Philippines, respectively (10). Even if there were no other sources of vitamin A in the diets, this boost in dietary beta-carotene could do much to prevent diseases associated with VAD.

GR is also financially viable. In Bangladesh, the current practice of fortifying rice with vitamin A and zinc using food additives, although supported by the World Food Programme, increases the cost of rice by 5% to 6% and is applied to only about 1 million metric tonnes of rice of the roughly 25 million metric tonnes produced in Bangladesh per year (11). GR, by contrast, poses no extra cost to governments, growers, or consumers in comparison with white rice.

Meanwhile, VAD has continued to cause severe illness and death among certain populations worldwide, especially children (12). The total estimated deaths from VAD-related diarrheal diseases and measles in children under five years of age in 2013 was 94,500 and 11,200, respectively, totaling 105,700 deaths across the world (4). Had GR become a part of diets in vulnerable populations worldwide, a portion of these lives might have been saved. Hopefully, approval of the commercialization of GR in the Philippines will provide impetus for Bangladesh and other nations with high VAD rates to provide poor consumers with an option that may save lives and improve health.

Those who oppose transgenic or genetically modified organisms raised concerns that led policymakers to delay the approval of the technologies (13). One argument relates to biotechnology company profits. But because the GR technology to the public sector is available at no cost for humanitarian uses, this concern is irrelevant. There are no limitations, except export, on GR use: replanting or selling or giving away seed, or polishing for consumption or sale.

Greenpeace summarized a food security-related objection to GR in a 2012 statement (14): If introduced on a large scale, GR can exacerbate malnutrition and ultimately undermine food security. The implication: GR will worsen malnutrition because it leads to a diet based on one staple. However, the replacement of traditional rice with GR would not exclude the development of diversified diets; in the meantime, vitamin A status could improve for many in the population. And optimizing vitamin A delivery could improve public health in at-risk populations.

A reasonable objection concerns possible human or environmental health risks. The United Nations (UN) Cartagena Protocol on Biosafety (15) provides a framework for the regulation of genetically engineered crops in many countries, emphasizing the Precautionary Principle in assessing risks, and leaving out assessment of benefits. This Protocol was signed in 2000 and became effective in 2003, in the relatively early days of agricultural genetic engineering. Since then, multiple studies have reported on benefits of genetically modified organism (GMO) adoption through increased yields, reduced pesticide use, improved farmer income, reduced prices to consumers, and in some cases even improved food safety (16). Meanwhile, there have been no confirmed incidents of adverse human health or environmental effects from genetically engineered crops during nearly three decades of global use (16).

Transgenic crops are subject to many required regulatory tests before approval, including animal feeding and invitro studies for toxicity and allergenicity. Yet opponents of these crops have continued to amplify suspicion on the long-term health effects of genetically engineered crops (17). Protection against such risks can be achieved through monitoring of the performance and the impacts of technologies and intervening when setbacks occur. However, the food safety assessments for transgenic crops in many countries are more demanding than for conventionally bred varieties. In fact, often less is known about the properties of plants developed by conventional mutagenesis than those developed by transgenic methods.

Another concern is that GR genes may intermingle with those of conventionally bred rice varieties. This uncertainty, however, applies not just to GR but also to any other new rice variety. Humans have consumed rice for more than 4,000 years, including varieties that have been crossed genetically across multiple strains. Transgenic methods of introducing novel genes is not inherently of greater concern, unless those genes produce proteins with potential adverse health effectssomething that food safety tests for approval can determine. Clearly the lives saved with VAD outweigh concerns about these so-called unknown risks. In response to such criticisms, in 2016 more than 150 Nobel Laureates have signed an open letter to the UN, governments of the world, and Greenpeace, urging a more balanced approach toward genetically modified crops in general and GR in particular: Scientific and regulatory agencies around the world have repeatedly and consistently found crops and foods improved through biotechnology to be as safe as, if not safer than, those derived from any other method of production. Opposition based on emotion and dogma contradicted by data must be stopped (18).

The arguments used by organizations to delay adoption of GR often resemble the arguments of anti-vaccination groups, including those protesting vaccines to protect against COVID-19. Some of the opponents of GR and agricultural biotechnology more generally see the introduction of GR as forcing the consumption of GMOs on the population. However, for the case of GR, consumers have the option of easily avoiding consumption because GR is very easily identifiable by its color.

The tragedy of GR is that regulatory delays of approval have immense costs in terms of preventable deaths, with no apparent benefit (13). The approval of GR is even more urgent with the ongoing pandemic, which has made access to healthcare services more difficult in vulnerable populations worldwide. The World Bank has recommended that micronutrient biofortification of staple crops, including specifically GR, should be the norm and not the exception in crop breeding (19).

Golden rice can effectively control VAD. Delaying the uptake of a genetically modified product shown to have clear health benefits has and will cost numerous lives, frequently of the most vulnerable individuals. Policymakers must find ways to overcome this resistance and accelerate the introduction and adoption of Golden Rice.

December 23, 2021: The article text has been updated.

Author contributions: J.W., D.Z., and A.D. designed research; F.W., J.W., C.C., and A.D. performed research; F.W., J.W., and C.C. analyzed data; and F.W., J.W., D.Z., R.R., C.C., and A.D. wrote the paper.

Competing interest statement: A.D. is a member and the Executive Secretary of the Golden Rice Humanitarian Board. He is a volunteer, unpaid and without grants. R.R. is a member of the Golden Rice Humanitarian Board. He is a volunteer, unpaid and without grants. The Golden Rice Humanitarian Board (http://www.goldenrice.org) holds the rights for humanitarian applications of the nutritional technology created by Professors Ingo Potrykus and Peter Beyer and related licensed technology. The Board is not legally incorporated in any way. It is a group of individuals who voluntarily share the objective of making Golden Rice available to resource-poor populations as a public good, delivered by the public sector in locally adapted and preferred rice varieties, at no greater cost than white rice and with no use limitations except export. All other authors declare no competing interests.

Any opinions, findings, conclusions, or recommendations expressed in this work are those of the authors and do not necessarily reflect the views of the National Academy of Sciences.

*Many transformation events were produced (8), from which event GR2E has been selected on the basis of molecular structure and insertion in the rice genome, together with agronomic performance. It is the basis of the regulatory data generated and is the only form of GR which is offered for approval and use.

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RNA and DNA Extraction Kit Market Study | Know the Post-Pandemic Scenario of the Industry – BioSpace

Posted: December 24, 2021 at 2:31 am

RNA and DNA extraction plays a crucial role in cancer genetic studies, which involves mutation analysis, comparative genomic hybridization, and microsatellite analysis. The rising incidences of cancer globally are creating a need for the advanced RNA and DNA extraction kit and are expected to drive market growth in the coming years.

Based on the product, the market is expected to segregate into RNA extraction kit and DNA extraction kit. Of these, the DNA extraction kit segment is expected to account for the leading share in the overall RNA and DNA extraction kit market. Additionally, the applications of DNA extraction kits mainly in the genetic engineering of animals and plants in pharmaceutical manufacturing. This is expected to fuel growth of RNA and DNA extraction kit market.

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Global RNA and DNA Extraction Kit Market: Notable Developments

Some of the most prominent competitors operating in the competitive landscape of global RNA and DNA extraction kit market include

Global RNA and DNA Extraction Kit Market: Drivers and Restraints

The rise and progress in customized drug have helped social insurance experts create exact sub-atomic focused on treatment dependent on a person's hereditary cosmetics and prescient information explicit to patients. The advancement of customized medication requires genome-mapping investigations of separated cells, which can be completed with the assistance of DNA and RNA extraction kits. DNA extraction kits are utilized to recognize quality polymorphisms identified with sickness or medication digestion though RNA extraction kits are utilized to break down RNA combination in separated cells. With the expanding appropriation of customized prescription, the demand for RNA and DNA extraction kits will likewise develop.

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There is a developing rate of malignant growth over the globe. The inside and out understanding of tumor hereditary qualities given by trend-setting innovations in malignant growth research has empowered the advancement of novel treatments to battle disease-causing qualities. The virtue, amount, and nature of separated RNA assume a huge job in the accomplishment of RNA examination and examination and consequent capacity of specific quality articulation. RNA extraction likewise helps in recognizing circulating tumor cells (CTCs) and non-intrusive observing of cutting edge malignant growths.

Global RNA and DNA Extraction Kit Market: Regional Outlook

On the basis of region, the RNA and DNA extraction kit market is segmented into North America, Europe, Latin America, Asia Pacific, and the Middle East & Africa. Of these, North America is expected to dominate the global RNA and DNA extraction kit market owing to robust innovation procedures running in the region. This factor is expected to offer robust growth opportunities to key players in RNA and DNA extraction kit market. Additionally, increasing demand for the automated systems coupled with the rising need for the RNA and DNA extraction kit across the extraction kits especially in the medical diagnosis is expected to drive growth of the market in coming years.

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Aridis Pharmaceuticals Announces a Pan-Coronavirus Monoclonal Antibody Cocktail That Retains Effectiveness Against the Omicron variant, other COVID-19…

Posted: December 24, 2021 at 2:31 am

LOS GATOS, Calif., Dec. 21, 2021 /PRNewswire/ -- Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS), a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, announced today that its fully human monoclonal antibody (mAb) cocktail AR-701 is broadly reactive against the Omicron and other COVID-19 (SARS-CoV-2) variants, SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome Coronavirus), and seasonal ('common cold') human coronaviruses.

"Omicron has rendered current COVID-19 vaccines and monoclonal antibodies substantially less effective, and likely future COVID 19 variants will arise that continue this trend" said Vu Truong, Ph.D., Chief Executive Officer of Aridis Pharmaceuticals. "AR-701 is the result of our successful search for a mAb therapy that is directed against a conserved region of the virus that would be less vulnerable to mutations and new variants such as Omicron. Our laboratory data suggest that AR-701 has the potential to be a future-proof COVID-19 therapy that can protect against SARS-CoV-2, SARS, or MERS pandemics," continued Dr. Truong. "To our knowledge AR-701 is the only COVID-19 therapy that targets two distinct viral mechanisms of action, making it much harder for the virus to generate resistance, and exhibits an unmatched combination of broad reactivity and high efficacy," continued Dr. Truong.

About AR-701AR-701 is a cocktail of two fully human immunoglobulin G1 (IgG1) mAbs discovered from screening the antibody secreting B-cells of convalescent SARS-CoV-2 infected (COVID-19) patients. AR-701 consists of AR-703 and AR-720 mAbs, each neutralizes coronaviruses using distinct mechanisms of action, namely inhibition of viral fusion and entry into human cells (AR-703) and blockage of viral binding to the human 'ACE2' receptor (AR-720). The two mAbs complement and enhance each other in a synergistic fashion, creating a potent first-in-class cocktail. AR-703 binds to the 'S2' stalk region of spike proteins from betacoronaviruses, including the SARS-CoV2 variants (beta, gamma, delta, epsilon), and binds to the Omicron variant with no loss in affinity compared to the original Wuhan strain. Multiple animal challenge models widely used to evaluate COVID-19 treatments support AR-701's broad efficacy, including:

The AR-701 mAbs are engineered to be active for 6-12 months in the blood. AR-701 is being developed as a long-acting intramuscular as well as a self-administered inhaled formulation for the treatment of COVID-19 patients who are not yet hospitalized. AR-701 mAbs were discovered through a collaboration with researchers at the University of Alabama in Birmingham and Texas Biomedical Research Institute (San Antonio, TX).

About Aridis Pharmaceuticals, Inc.

Aridis Pharmaceuticals, Inc. discovers and develops novel anti-infective therapies to treat life-threatening infections, including anti-infectives to be used as add-on treatments to standard-of-care antibiotics. The Company is utilizing its proprietary PEXTM and MabIgX technology platforms to rapidly identify rare, potent antibody-producing B-cells from patients who have successfully overcome an infection, and to rapidly manufacture monoclonal antibody (mAbs) for therapeutic treatment of critical infections. These mAbs are already of human origin and functionally optimized for high potency by the donor's immune system; hence, they technically do not require genetic engineering or further optimization to achieve full functionality.

The Company is advancing multiple clinical stage mAbs targeting bacteria that cause life-threatening infections such as ventilator associated pneumonia (VAP) and hospital acquired pneumonia (HAP), in addition to preclinical stage antiviral mAbs. The use of mAbs as anti-infective treatments represents an innovative therapeutic approach that harnesses the human immune system to fight infections and is designed to overcome the deficiencies associated with the current standard of care which is broad spectrum antibiotics. Such deficiencies include, but are not limited to, increasing drug resistance, short duration of efficacy, disruption of the normal flora of the human microbiome and lack of differentiation among current treatments. The mAb portfolio is complemented by a non-antibiotic novel mechanism small molecule anti-infective candidate being developed to treat lung infections in cystic fibrosis patients. The Company's pipeline is highlighted below:

Aridis' Pipeline

AR-301 (VAP). AR-301 is a fully human IgG1 mAb targeting gram-positive Staphylococcus aureus (S. aureus) alpha-toxin and is being evaluated in a global Phase 3 clinical study as an adjunctive treatment of S. aureus ventilator associated pneumonia (VAP).

AR-320 (VAP). AR-320 is a fully human IgG1 mAb targeting S. aureus alpha-toxin that is being developed as a preventative treatment of S. aureus colonized mechanically ventilated patients who do not yet have VAP. Phase 3 is expected to be initiated in 2Q22.

AR-501 (cystic fibrosis). AR-501 is an inhaled formulation of gallium citrate with broad-spectrum anti-infective activity being developed to treat chronic lung infections in cystic fibrosis patients. This program is currently in Phase 2a clinical development in CF patients.

AR-701 (COVID-19). AR-701 is a cocktail of fully human mAbs discovered from convalescent COVID-19 patients that are directed at multiple protein epitopes on the SARS-CoV-2 virus. It is formulated for delivery via intramuscular injection or inhalation using a nebulizer. AR-701 replaces AR-712 as the company's leading COVID mAb candidate.

AR-401 (blood stream infections). AR-401 is a fully human mAb preclinical program aimed at treating infections caused by gram-negative Acinetobacter baumannii.

AR-101 (HAP). AR-101 is a fully human immunoglobulin M, or IgM, mAb in Phase 2 clinical development targeting Pseudomonas aeruginosa (P. aeruginosa) liposaccharides serotype O11, which accounts for approximately 22% of all P. aeruginosa hospital acquired pneumonia cases worldwide.

AR-201 (RSV infection). AR-201 is a fully human IgG1 mAb out-licensed preclinical program aimed at neutralizing diverse clinical isolates of respiratory syncytial virus (RSV).

For additional information on Aridis Pharmaceuticals, please visit https://aridispharma.com/.

Forward-Looking Statements

Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. These statements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Aridis' expectations, strategy, plans or intentions. These forward-looking statements are based on Aridis' current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the need for additional financing, the timing of regulatory submissions, Aridis' ability to obtain and maintain regulatory approval of its existing product candidates and any other product candidates it may develop, approvals for clinical trials may be delayed or withheld by regulatory agencies, risks relating to the timing and costs of clinical trials, risks associated with obtaining funding from third parties, management and employee operations and execution risks, loss of key personnel, competition, risks related to market acceptance of products, intellectual property risks, risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm our financial condition and increase our costs and expenses, risks associated with the uncertainty of future financial results, Aridis' ability to attract collaborators and partners and risks associated with Aridis' reliance on third party organizations. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described under the caption "Risk Factors" in Aridis' 10-K for the year ended December 31, 2020 and Aridis' other filings made with the Securities and Exchange Commission. Forward-looking statements included herein are made as of the date hereof, and Aridis does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Contact:Media Communications:Matt SheldonRedChip Companies Inc.Matt@redchip.com1.917.280.7329

Investor RelationsDave GentryRedChipDave@redchip.com1-800-733-2447

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Company Codes: NASDAQ-NMS:ARDS

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