Category Archives: Genetics

The video shows a discussion on genome-editing technique rather than an mRNA procedure. mRNA isnt even mentioned once in the entire video.

Context:

While the world continues to deal with the impact of COVID-19, misleading posts accompanying a 2.17 minutes-long video are doing the rounds over social media spreading misinformation about mRNA COVID-19 vaccines by linking them to a genome-editing technology. One such Facebook post is titled WEF video from 2015 discussing the ability of an mRNA medical procedure to permanently change the genetics of the subject and its offspring. Similar posts include a screengrab of the video and make references to COVID-19 vaccines. What do you think they were really doing with all these covid shots? further asked the post. Such posts aim to instill suspicion and fear in the viewers minds about the technology used in COVID-19 vaccines.

In fact:

The 2.17 minutes-long video being circulated on social media begins with the speaker stating, So this is a precision tool that now allows us to take this protein RNA complex and introduce it into cells or tissues.

It appears that the term RNA has been erroneously misinterpreted as mRNA. In addition, we found an extended version of the video,which is 5.25 minutes-long, on the World Economic Forums official YouTube channel, and the video does not mention mRNA even once.

In the video, University of California professor Jennifer Doudna discusses RNA therapies and DNA editing breakthroughs in 2015 at a World Economic Forum(WEF) event. The CRISPR-Cas9 co-discoverer Doudna describes how the technology can alter DNA and offers the possibility of curing human genetic disorders. Professor Doudna has won the 2020 Nobel Prize in Chemistry along with Professor Emmanuelle Charpentier for discovering the gene-editing technique (CRISPRCas9).In the video, she says that compared to what a word processor does for writing, the technique allows for modifying genomic code in living organisms. Doudna claims that they discovered Cas9, a protein that can be designed to split double-stranded DNA, repair breaks, and correct genetic mutations.

According to Medline Plus, CRISPR-Cas9 is an acronym for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. According to the National Human Genome Research Institute, the genome is the entire set of DNA instructions found in a cell. An individuals genome contains all the information needed for growth and function.

National Cancer Institute defines an mRNA as a particular form of RNA. mRNA molecules transfer the data from the DNA in the cells nucleus to the cytoplasm, where proteins are made. However, the CRISPR-Cas9 system involves guide RNA (gRNA). Furthermore, mRNA is not even mentioned in the original paper published on the subject in Science in 2012.

Medline Plus notes that ethical concerns are often raised when human genomes are edited using tools like CRISPR-Cas9. This DNA editing technology is being investigated for several diseases, including single-gene disorders, in research and clinical trials. Contrary to claims on social media, only particular tissues are affected by the modifications, which are not transferred from generation to generation unless the gene alterations are in the egg, sperm, or embryonic cells. Only in such cases, may the changes be passed on to succeeding generations.

Thus, it is evident that there is no relation between COVID-19 vaccines and genome editing technology as these two technologies are entirely different. Conspiracy theorists have constantly claimed that COVID-19 vaccines were meant to alter human DNA among other bogus claims. These false claims have been repeatedly debunked by Logically and other independent fact-checkers in the past.

The verdict:

The video is about DNA editing techniques and not an mRNA procedure. Some fallacious social media posts linking this technology to COVID-19 vaccines merely show a small portion of the entire video. The authorized mRNA COVID-19 vaccines do not use the gene editing method being explained in the video. Thus, we mark this claim misleading.

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Fact Check: A video from 2015 discusses the ability of an mRNA medical procedure to change the genetics of - The Paradise News

The Biobank provides DNA specimens for personalized medicine treatments and research. Photo: Getty Images.

A fundamental financial concept is that banks should be well capitalized with diversified investment portfolios. These two elements are the foundation of their economic strength.

In genetics, a different kind of bank must adhere to a similar set of principles in its own unique way.

On the Anschutz Medical Campus, thats the Biobank, which is part of the Colorado Center for Personalized Medicine. The Biobank is a repository of DNA specimens from UCHealth and Childrens Hospital Colorado patients. Researchers use the samples for research, genetic analysis and clinical care. The bank is one key element in efforts to advance personalized or precision medicine that aims to tailor medical care to the specific genetic makeup of patients.

But as with the banks with teller windows and ATMs, the Biobank and other biorepositories like it need deposits and the more the better, says Dr. David Kao, medical director of the Colorado Center for Personalized Medicine. The deeper the biorepository, the greater the evidence on which to learn from and draw reliable conclusions about, for example, specific genetic mutations and the health conditions linked to them.

The fewer the people, the more generic the treatments, Kao said. The more people, the more targeted or personalized are the treatments.

In addition, Kao said, biobanks grow stronger as they diversify genetically. A repository that accurately reflects a communitys makeup is well positioned to assist clinicians and researchers in serving that community. Call it a well-diversified genetic portfolio.

For these reasons, Kao and his colleagues are working to reach out to UCHealth patients and the wider Colorado community to encourage people to participate in the Biobank. In an interview with UCHealth Today, Kao explained what the Biobank is, how it operates, and how it benefits both patients and providers. He also addressed questions about how the Biobank protects patient privacy.

The Biobank is essentially a large research study that aims to collect DNA specimens from a set of UCHealth and Childrens Hospital Colorado patients who voluntarily agree to participate.

The fundamental goal is to understand how genetics fits into everyday health, Kao said. We can learn how patients genes are associated with different facets of health, whether that is risk of developing certain conditions, or responses to treatment, or ways to prevent disease, Kao said.

To do that, biobanks strive to increase the number of specimens in the repository. Doing so enriches the genetic diversity of the specimens. That, in turn, helps researchers and clinicians learn more about the unique characteristics of patients in different racial and ethnic groups, for example.

A surprising amount of what we know about genes and diseases has come from a relatively narrow population of people white males, Kao explained. That is not the world, so we have discovered that the diversity that exists is important to study in order to know if the recommendations we are making are appropriate in different populations.

There are several reasons that it makes sense to have a local biobank, Kao said.

The first is that having a unique, local biobank helps with the practical goal of incorporating genetics into health care. The Biobank at the Colorado Center for Personalized Medicine contains samples and genetic information derived from UCHealth patients. That can enrich the knowledge their providers use to treat them.

We are able to assess how genetics are important to treating our patients here, Kao said. We can tell providers what the best things to do are, with confidence that it applies to the person in front of them.

For example, Kao said, Hispanics make up about 15% of UCHealths patient population. Genetic information from a biobank of patients from, say, the United Kingdom, with a much smaller Hispanic population, would not make an ideal match.

You know youre going to miss something, he said.

In addition, the Biobank specimen data links to a deep reservoir of clinical data stored in the Epic electronic health record (EHR), a capability many other institutions lack, Kao said.

Finally, the Biobank is set up to return certain clinical results from DNA specimens to patients. To our knowledge, we are the only biobank that does that, Kao said. Genetic research benefits everyone, but here you can get an individual benefit.

There are three main ways that the Biobank can help individual patients, Kao said.

First, there are a set of about 75 genes with significant health implications, most notably breast and other cancers and heart failure caused by organ deterioration that begins at a young age.

These are conditions that the genetics community has said, If you see this, you really need to tell the person, Kao said.

About 60 UCHealth patients with these genes have been identified, with about half so far contacted directly to notify them and help them make further decisions, he said.

Second, data about genes that affect how certain medications work or dont work go directly into a patients medical record in the EHR. If a provider tries to prescribe one of these medications, a message pops up with a warning about the patients genetic risk.

One example, Kao said, is statins, a frequently prescribed class of medications that protect against heart disease. In patients with a specific genetic abnormality, the drugs can cause muscle aches and soreness. Without understanding the genetic cause, the patient might stop taking the drug and increase their risk of heart problems. On the other hand, if the provider knows a specific drug has those side effects, theyll simply choose a different one.

We can make sure the person gets the medication they need without being misled by side effects, Kao said. He added that as of recently, the Biobank provides genetically driven advice for all statins because they are so commonly prescribed.

Third, genetic data has been used to flag other conditions, such as risk of hemochromatosis, or iron overload. The condition generally doesnt produce symptoms early, but over time, it can cause deposits of the mineral in the liver, heart and joints. A specific gene is usually present in people who have hemochromatosis, Kao said, although not everyone who has the gene will develop problems. But with knowledge of the gene, again embedded in the EHR, providers can advise patients to get screened early and, if necessary, get treatments, which are effective.

Without the genetic information, most patients wouldnt think to check about iron levels at an early age, Kao said.

Specimens are protected through the same protocols used to store other research specimens across the University of Colorado Anschutz Medical Campus, Kao said. They are placed in tubes with no patient identifying information and stored in deep freezers behind multiple locked doors, with access limited to very specific personnel, he added.

The data lives in a highly secured, cloud storage environment that is more secure than the electronic health record, Kao said. The specific genetic data is stored without patient identifying information attached to it.

It is true that for people with the specific genes discussed earlier (and others), the Biobank has a matching process used to regenerate the connection between them and their samples, Kao said. So we do have a path to trace genetic data back to an individual, because that is how we are able to put specific results back into the medical record. However, he added, that path involves several steps that are each secure in their own right. A hacker would have to breach all the systems involved and then know the protocols to rematch genetic data to an individual, and there are a number of safeguards to protect that from happening, Kao said.

Some researchers on campus use the results of the Biobanks analysis of DNA specimens, Kao said. Others may use samples for further testing in pursuit of their own research. But they have no access to patient-identifying information, he added.

Yes, some do. But, there is always rigorous protection of patient privacy, Kao said.

We collaborate with a number of national and international consortia of biobanks for research and innovation, he said. One purpose is to study conditions that might be seen infrequently in a place like Colorado or another state, region or country. With a much larger pool of biobank data, we can make some conclusions about relatively rare conditions, Kao said.

Dr. Chris Gignoux, director of research for the Colorado Center for Personalized Medicine, said the Biobank is part of consortia that include the Covid-19 Human Genetics Initiative, the Global Biobank Meta-analysis Initiative, and the Biobank Rare Variant Analysis consortium. Gignoux added that the Biobank works frequently with UCLA (ATLAS) and Mount Sinai (BioMe), and is now collaborating with those two biorepositories on three major grants. The Biobank also shares data with the Million Veteran Program and Vanderbilt University (BioVU), among others, he said.

The simplest way is to sign in to your My Health Connection account (or create one). Click the UCHealth Research Opportunities button on the main page to read more about the Biobank and view the consent form. After reading the form, you can sign it, decline to or elect to decide at a later time.

At your next clinic or hospital visit that requires a blood draw, a provider will draw at least one extra tube of blood. Kao said the Biobank has started more recently to use saliva-based collection, and mailed out 250 kits in early June. We may be ramping that up, he said.

Its important to be part of the research because the more different people that we have, both in terms of genes and their entire life course, the better we can understand how to customize, select and choose with each person how they want to treat disease or manage their health over time, Kao said.

Kao added that as medical director of the Biobank, he wants genetic medicine to become an accepted part of all medicine. I want more patients and providers to be aware of it and expect it, just like getting your blood sugar checked, he said. Part of that is empowering patients to learn about and figure out how to use the Biobank, how it matters to them and how they want to engage with it.

The rest is here:
Biobanking makes genetics a fundamental part of health care - UCHealth Today

We have long been baffled as to why men live around five years less than women, on average. But now a new study suggests that, beyond the age of 60, the main culprit is a genetic defect: the loss of the Y chromosome, which determines sex at birth.

Its clear that men are more fragile, the question is why, explains Lars Forsberg, a researcher at Uppsala University in Sweden.

For decades it was thought that the male Y chromosomes only function was to generate sperm that determine the sex of a newborn. A boy carries one X chromosome from the mother and one Y from the father, while a girl carries two Xs, one from each parent.

In 1963, a team of scientists discovered that as men age, their blood cells lose the Y chromosome due to a copying error that happens when the mother cell divides to produce a daughter cell. In 2014, Forsberg analyzed the life expectancy of older men based on whether their blood cells had lost the Y chromosome, a mutation called mLOY. The effect recorded was mindblowing, the researcher recalls.

Men with fewer Y chromosomes had a higher risk of cancer and lived five and a half years less than those who retained this part of the genome. Three years later, Forsberg discovered that this mutation makes getting Alzheimers three times as likely. What is most worrying is the enormous prevalence of this defect. Twenty percent of men over the age of 60 have the mutation. The rate rises to 40% in those over 70 and 57% in those over 90, according to Forsbergs previous studies. It is undoubtedly the most common mutation in humans, he says.

Until now, nobody knew whether the gradual disappearance of the Y chromosome in the blood played a pivotal role in diseases associated with aging. In a study just published in the journal Science, Forsberg and scientists from Japan and the US demonstrate for the first time that this mutation increases the risk of heart problems, immune system failure and premature death.

The researchers have created the first animal model without a Y chromosome in their blood stem cells: namely, mice modified with the gene-editing tool CRISPR. The study showed that these rodents develop scarring of the heart in the form of fibrosis, one of the most common cardiovascular ailments in humans, and die earlier than normal mice. The authors then analyzed the life expectancy recorded in nearly 15,700 patients with cardiovascular disease whose data are stored in the UK public biobank. The analysis shows that loss of the Y chromosome in the blood is associated with a 30% increased risk of dying from cardiovascular disease.

This genetic factor can explain more than 75% of the difference in life expectancy between men and women over the age of 60, explains biochemist Kenneth Walsh, a researcher at the University of Virginia in the US and co-author of the study. In other words, this mutation would explain four of the five years lower life expectancy in men. Walshs estimate links to a previous study in which men with a high mLOY load live about four years less than those without it.

It is well known that men die earlier than women because they smoke and drink more and are more prone to recklessness. But, beyond the age of 60, genetics becomes the main culprit in the deterioration of their health: It seems as if men age earlier than women, Walsh points out.

The study reveals the molecular keys to the damage associated with the mLOY mutation. Within the large group of blood cells can be found the immune systems white blood cells responsible for defending the body against viruses and other pathogens. The loss of the Y chromosome triggers aberrant behavior in macrophages, a type of white blood cell, causing them to scar heart tissue, which in turn increases the risk of heart failure. Researchers have shown that the damage can be reversed if they give mice pirfenidone, a drug approved to treat humans with idiopathic pulmonary fibrosis, a condition in which the lungs become scarred and breathing becomes increasingly difficult.

There are three factors that increase the risk of Y chromosome loss. The first is the inevitable ageing process. The longer one lives, the more cell divisions occur in the body and the greater the likelihood of mutations occurring in the genome copying process. The second is smoking. Smoking causes you to lose the Y chromosome in your blood at an accelerated rate; if you stop smoking, healthy cells once again become the majority, says Walsh. But the third is also inevitable: other inherited genetic mutations can increase the gradual loss of the Y chromosome in the blood by a factor of five, explains Forsberg.

Both Forsberg and Walsh believe that this study opens up an enormous field of research. Still to be studied is whether men with this mutation also have cardiac fibrosis and whether this is behind their heart attacks and other cardiac ailments. We also need to better understand why losing the Y chromosome damages health. For now, we have shown that the Y chromosome is not just there for reproduction, but is is also important for our health, says Forsberg. The next step is to identify which genes are responsible for the phenomenon.

The loss of this chromosome has been detected in all organs and tissues of the body and at all ages, although it is more evident after 60. It is abundant in the blood because this is a tissue that produces millions of new cells every day from blood stem cells. Healthy stem cells produce healthy daughter cells and mutated ones produce daughter cells with mLOY.

A previous study showed that this mutation of the Y chromosome disrupts the function of up to 500 genes located elsewhere in the genome. It has also been shown to damage lymphocytes and natural killer cells, evident in men with prostate cancer and Alzheimers disease, respectively.

There are hardly any tests for mLOY at present. But Forsberg and his colleagues have designed a PCR test that measures the level of this mutation in the blood and could serve to determine which levels of this mutation are harmful to health. Right now, we see people in their 80s with 80% of their blood cells mutated, but we dont know what impact this has on their health, says Walsh.

Another unanswered question is why men lose the genetic mark of the male with age. The evolutionary logic, argue the authors of the paper, is that men are biologically designed to have offspring as soon as possible and to live 40 to 50 years at most. The spectacular increase in life expectancy in the last century has meant that men and women live to an advanced age 80 and 86 years in Spain, respectively which makes the effect of these mutations more evident. Another fact which possibly has some bearing on the issue: the vast majority of people who reach 100 are women.

To transform all these discoveries into treatments, we first need to better understand this phenomenon, says Forsberg. We men are not designed to live forever, but perhaps we can increase our life expectancy by a few more years.

Biochemist Jos Javier Fuster, who studies pathological mutations in blood cells at the National Center for Cardiovascular Research, stresses the importance of the work. Until now it was not clear whether the loss of Y was the cause of cancer, Alzheimers disease and heart failure, he explains. This is the first demonstration in animals that it has a causal role. The human Y chromosome is different from the mouse chromosome, so the priority now is to accumulate more data in humans. This is a great first step in understanding this new mechanism behind aging-linked diseases, he adds.

The cells of the human body group their DNA into 23 pairs of chromosomes that pair up one by one when a cell copies its genome to generate a daughter cell. The Y is the only one that does not have a symmetrical partner to pair up with: instead, it does so with an X chromosome; and the entire Y chromosome is often lost, explains Luis Alberto Prez Jurado from Pompeu Fabra University in Barcelona. For now, six genes have been identified within the Y chromosome that would be responsible for an impact on health, he says. All of them are related to the proper functioning of the immune system. In part, this would also explain the greater vulnerability of males to viral infections, including Covid-19.

Originally posted here:
mLOY: The genetic defect that explains why men have shorter lives than women - EL PAS USA

Media Advisory

Thursday, July 14, 2022

Researchers from the National Cancer Institute, part of the National Institutes of Health, and their collaborators have discovered that people of European and African ancestries who were hospitalized for COVID-19 are more likely to carry a particular combination of genetic variants in a gene known as OAS1 than patients with mild disease who were not hospitalized. People with this combination of genetic variants also remain positive for SARS-CoV-2 infection longer. However, interferon treatment may reduce the severity of COVID-19 in people with these genetic factors. Interferons are a type of protein that can help the bodys immune system fight infection and other diseases, such as cancer.

The study appears July 14 in Nature Genetics.

These findings build on previous studies that have suggested that genetic factors, such as genetic variants affecting OAS antiviral proteins that facilitate the detection and breakdown of the SARS-CoV-2 virus, may influence the risk of SARS-CoV-2 infection.

The NCI researchers and their collaborators found that treatment of cells with an interferon decreased the viral load of SARS-CoV-2. The researchers also analyzed data from a clinical trial in which patients with COVID-19 who were not hospitalized were treated with the recombinant interferon pegIFN-1 and found that treatment improved viral clearance in all patients; those with the OAS1 risk variants benefitted the most. The results suggest that interferon treatment may improve COVID-19 outcomes and specifically in patients with certain OAS1 genetic variants who have impaired ability to clear infection.

Ludmila Prokunina-Olsson, Ph.D., and Oscar Florez-Vargas, Ph.D., Division of Cancer Epidemiology and Genetics, National Cancer Institute

Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries appears July 14 in Nature Genetics.

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIHs efforts to dramatically reduce the prevalence of cancer and improve the lives of people with cancer. NCI supports a wide range of cancer research and training extramurally through grants and contracts. NCIs intramural research program conducts innovative, transdisciplinary basic, translational, clinical, and epidemiological research on the causes of cancer, avenues for prevention, risk prediction, early detection, and treatment, including research at the NIH Clinical Centerthe worlds largest research hospital. Learn more about NCIs intramural research from the Center for Cancer Research and the Division of Cancer Epidemiology and Genetics. For more information about cancer, please visit the NCI website at cancer.gov or call NCIs contact center at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Interferon treatment may reduce severity of COVID-19 in people with certain genetic factors - National Institutes of Health (.gov)

Exiting non-core businesses and geographies to prioritize higher-margin business initiatives

Expects to deliver approximately $326million in non-GAAP annualized cost savings in 2023

Provides preliminary revenue and gross margin ranges for the second quarter of 2022; amends full-year 2022 financial guidance

Conference call and webcast today at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time

SAN FRANCISCO, July 18, 2022 /PRNewswire/ -- Invitae (NYSE: NVTA), a leading medical genetics company, today announced a comprehensive plan to realize the full potential of its industry-leading genetics platform. The plan introduces a significant realignment of the company's operations in support of business lines and geographies that generate sustainable margins, provide the best return to fuel future investment and accelerate the company's path to positive cash flow. The plan further helps ensure Invitae remains at the forefront of innovation and advancements in genomics by allocating resources towards the company's core genome sequencing and genome management platforms that have the potential to improve healthcare outcomes.

Invitae's (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. http://www.invitae.com (PRNewsFoto/Invitae Corporation)

The operational realignment includes streamlining and cost reduction programs that are expected to deliver approximately $326 million in annualized cost savings to be fully realized by 2023 and extend the company's cash runway to the end of 2024.

In a separate press release issued earlier today, Invitae announced executive and board-level transitions to lead the company in this next phase and achieve its mission of bringing the power of genetic information to mainstream medicine.

Kenneth D. Knight, Invitae's CEO, said, "We are at a unique, transitional moment in the rapidly-evolving genomics industry when companies that balance accessible, trusted and cutting-edge genomic information with disciplined operational excellence will be in a far stronger position to thrive and deliver transformative healthcare outcomes. This operational imperative is at the center of the plan we announced today, which will advance several critical objectives and is intended to drive long-term profitable growth. First, our refocused and realigned platform will allocate resources where they should be: at our core, we are a growth-oriented genomic testing platform. Second, aggressive actions to substantially reduce spend over the coming 12-18 months will improve operating leverage and align Invitae's cost structure with current market dynamics and the broader economy. These adjustments will meaningfully extend our cash runway and accelerate the pursuit of our long-term growth targets and positive cash flow. Most importantly, the plan reaffirms our commitment to leading the way in shaping the future of medicine through powerful genomic tools."

Story continues

Mr. Knight continued, "Invitae's new operating plan has far-reaching and for many of our dedicated, hard-working team members difficult implications, and we regret that impact. Invitae is committed to working closely and compassionately with those adversely affected to help ensure as smooth a transition as possible, and we thank everyone on our team for their contributions. As we look to that future, we are as committed as ever to driving forward our mission and advancing the kind of transformative healthcare that is Invitae's core."

Operating Plan Overview

At a high level, Invitae will eliminate non-core operations while realigning and sharpening its focus on the portfolio of businesses that generate sustainable margins and deliver returns to fuel future investment.In the testing business, Invitae will shift operational and commercial efforts to accelerate positive cash flow by maintaining robust support of the higher-margin, higher-growth testing opportunities among oncology, women's health, rare disease and pharmacogenomics. The company also plans to continue its expansion and integration of key digital health-based technologies and services in order to create a differentiated model in genetic health. Longer-term, Invitae remains committed to its genomic management business. The company believes that it holds outsized growth potential and intends to continue to prioritize the tools, partnerships and applications that support the development of genome management as the catalyst for the future of healthcare.

Operating Plan Details

Headcount and office/lab space: The company plans workforce reductions aligned with its newly-streamlined operations. The company is also taking immediate steps to consolidate underutilized office and laboratory space.

Portfolio optimization:The company has conducted a rigorous assessment of its product portfolio as well as the associated research & development and commercial spending. The new plan shifts the focus to programs relevant to the core testing businesses to drive near-term cost of goods sold (COGS) reductions. These programs will speed the pathway to positive cash flow and drive the completion of the genome management platform that places Invitae in the middle of patients, providers and the greater healthcare ecosystem. Initiatives and products that are not attached to the go-forward core priorities have been put on hold or eliminated.

Other operating expenses: The company has performed an extensive review of internal and external costs and how those may align with the new business structure. Through that analysis, additional savings will be generated through the ongoing digitization of workflows, elimination of duplication and streamlined processes across the core platforms and rationalization of technology and external services spend.

International business structure: As part of the plan announced today, the company will shift its focus to serving less than a dozen international geographies where the testing business demonstrates the potential to reach positive cash flow in a shorter duration. The company plans to conduct an orderly exit from territories and countries in which the business is more nascent, focusing on supporting those territories through the transition and allowing those providers and patients sufficient time to shift to alternative resources for their testing needs.

As noted, these changes are expected to deliver approximately $326 million in annual cost savings by the end of 2023 and allow the company to extend its cash runway to the end of 2024. Invitae will operate as a leaner, more focused organization, targeting both a stronger and more profitable testing services business as well as the completion and launch of a genome management platform, which will serve to allow patients, providers, and the entire healthcare ecosystem to utilize genomic information for a lifetime of better personal health decisions and outcomes.

Supporting the growth of the company's core testing and other commercial efforts remains a priority. The company will continue to drive its commercial efforts to best suit its differentiated platform offerings through a more efficient sales and marketing approach.

Preliminary Second Quarter Results

On a preliminary basis, the revenue for the quarter ended June 30, 2022 is approximately $136 million.

GAAP gross margin in the second quarter of 2022 is expected to be 18-19%. Non-GAAP gross margin is estimated to be 39-40%.

Cash, cash equivalents, restricted cash and marketable securities totaled around $737 million on June 30, 2022. Second quarter 2022 cash burn is estimated to be approximately $150 million.

Invitae has not completed preparation of its financial statements for the second quarter. The preliminary, unaudited results presented in this press release are based on current expectations and are subject to change. Actual results may differ materially from those disclosed in this press release.

Guidance

Invitae has updated its 2022 annual revenue guidance to reflect the preliminary first half results and the anticipated impacts of the actions announced today, which include the sale or wind down of non-core products and services and the elimination of certain international territories to focus on more profitable revenue streams. Revenue in the near term is anticipated to be flat in the second half of 2022 over the first half, representing a low double-digit growth rate for full year 2022 over 2021 despite the impacts of the strategic realignment. We expect 2023 to be an adjustment year and for longer term revenue growth rates to return to between 15% and 25% beyond 2023.

Invitae is maintaining its previous 2022 cash burn guidance of $600-650 million, which includes an estimated $75-100 million to be used for reorganization activities and severance. The company also anticipates its cash burn to be in the range of $225-275 million in 2023, or a $325-425 million reduction from expected 2022 cash burn.

Non-GAAP gross margins are expected to continue to increase for the rest of the year, based on ongoing margin improvement efforts and the current realignment initiatives, to the range of 42-43% for full year 2022.

Non-cash related charges are expected to be recorded in the third quarter of 2022 and in following quarters.

Webcast and Conference Call Details

Management will host a conference call and webcast today at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time to discuss today's announcements. To access the conference call, please register at the link below:

https://event.on24.com/wcc/r/3870686/DE684B93E9A64871E619579F0C45867A

Upon registering, each participant will be provided with call details and a conference ID.

The live webcast of the call and slide deck may be accessed here or by visiting the investors section of the company's website at ir.invitae.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the company's website.

About Invitae

Invitae Corporation (NYSE: NVTA) is a leading medical genetics company whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website at invitae.com.

Safe Harbor Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the expected impact, benefits, parameters, details and timing of the company's strategic business realignment or various aspects thereof; the company's beliefs regarding the potential of its business, and its business priorities; the company's preliminary financial results for the quarter ended June 30, 2022; the company's future financial and operating results, including estimated annual cost savings, cash runway, guidance for 2022 and beyond, and the drivers of future financial results; the company's beliefs regarding what is necessary to succeed in the industry; the company's focus for the remainder of 2022, and its expectations regarding future operating cash flows; and the company's expectations regarding its genome management platform and the benefits thereof. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: actual results for the quarter ended June 30, 2022; the ability of the company to successfully execute its strategic business realignment and achieve the intended benefits thereof on the expected timeframe or at all; unforeseen or greater than expected costs associated with the strategic business realignment; the risk that the disruption that may result from the realignment may harm the company's business, market share or its relationship with customers or potential customers; the impact of COVID-19 on the company, and the effectiveness of the efforts it has taken or may take in the future in response thereto; the impact of inflation and the economic environment on the company's business; the company's ability to grow its business in a cost-effective manner; the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the risk that the company may not obtain or maintain sufficient levels of reimbursement for its tests; the ability of the company to obtain regulatory approval for its tests; the applicability of clinical results to actual outcomes; the company's failure to successfully integrate or fully realize the anticipated benefits of acquired businesses; risks associated with litigation; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; laws and regulations applicable to the company's business; and the other risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2022. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Non-GAAP Financial Measures

To supplement Invitae's consolidated financial statements prepared in accordance with generally accepted accounting principles in the United States (GAAP), the company is providing several non-GAAP measures, including non-GAAP gross margin and non-GAAP cash burn. These non-GAAP financial measures are not based on any standardized methodology prescribed by GAAP and are not necessarily comparable to similarly-titled measures presented by other companies. Management believes these non-GAAP financial measures are useful to investors in evaluating the company's ongoing operating results and trends.

Management is excluding certain items from some or all of its preliminary non-GAAP operating results. These non-GAAP financial measures are limited in value because they exclude certain items that may have a material impact on the reported financial results. Management accounts for this limitation by analyzing results on a GAAP basis as well as a non-GAAP basis and also by providing GAAP measures in the company's public disclosures.

Cash burn also excludes certain items. Management believes cash burn is a liquidity measure that provides useful information to management and investors about the amount of cash consumed by the operations of the business. A limitation of using this non-GAAP measure is that cash burn does not represent the total change in cash, cash equivalents, and restricted cash for the period because it excludes cash provided by or used for other operating, investing or financing activities. Management accounts for this limitation by providing information about the company's operating, investing and financing activities in the statements of cash flows in the consolidated financial statements in the company's most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K and by presenting net cash provided by (used in) operating, investing and financing activities as well as the net increase or decrease in cash, cash equivalents and restricted cash in its reconciliation of cash burn.

In addition, other companies, including companies in the same industry, may not use the same non-GAAP measures or may calculate these metrics in a different manner than management or may use other financial measures to evaluate their performance, all of which could reduce the usefulness of these non-GAAP measures as comparative measures. Because of these limitations, the company's non-GAAP financial measures should not be considered in isolation from, or as a substitute for, financial information prepared in accordance with GAAP. Investors are encouraged to review the non-GAAP reconciliations for historical periods that will be provided on the company's website in connection with today's conference call.

Contacts for Invitae:

Investor Relations:Hoki Lukir@invitae.com

Public Relations:Amy Hadsockpr@invitae.com

Cision

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Invitae Announces Strategic Business Realignment to Accelerate Its Path to Positive Cash Flow and Realize Full Potential of Industry-Leading Genetics...

By Jacob Mosenda

Dar es Salaam. Pharmacists have reiterated the need for technological reforms in the distribution of drugs based on the patient's genetics to fight drug resistance that is currently plaguing the world.

According to the new drug manufacturing technology, there are drugs that enable the patient to be treated for the type of disease he or has even if he has developed drug resistance.

The call was made on Saturday July 16, at the 10th African Pharmaceutical Symposium (AfPS) under the theme"Pharmaceutical evolution in the era of technological advancement, the present and the future"and brought together the students in the cadre from 13 African countries.

The chairperson of the Tanzania Pharmaceutical Students Association (TAPSA), Ms Arafa Khamis, said that most patients use drugs without following the procedures prescribed by the doctor or pharmacist and in the end create drug resistance.

"If we make medicine according to the current technology and since many people are resistant to it, then we can treat people with any type of disease and get positive results whether they are resistant to the medicine or not, she said.

Right now, she said there were many companies manufacturing drugs abroad, and Tanzania was mostly importing, yet most of the pharmacists do not know such a technology, they are still using the same drugs even patients show resistance.

"It is important for the government to train them and if they could make medicine according to new technology, we would succeed in fighting resistance," she further noted.

Media and publication officer at TAPSA, Isack Nyaimaga called on the government to improve access to friendly infrastructure that will enable pharmacists to manufacture drugs in the country using new technology.

This, he said, will reduce the importation of drugs from abroad and bring development and employment to pharmacists in the country.

"We expect this cadre to be used in manufacturing medicines that will treat people according to their genetics using technology, if you are told that this medicine has failed according to certain genetics, the alternatives should be available," he said.

For her part, Ms Fiona Chilunda, the senior drug advisor from the Health Promotion and System Strengthening (HPSS)Tuimarise AfyaProject asked the government to increase the number of pharmacists in health centres in order to enhance proper use of drugs in the country and bring the real value of the drug budget set every fiscal year.

She said that currently there are many pharmacists produced in the country (without mentioning the statistics) so they can meet the needs of the country.

"The government should increase its capacity for pharmacists, every year the government adds a large amount of money to the drug budget, I want them to think about how to increase the staff of this cadre so that the drugs are used correctly. We need to have enough of them in all areas of health services," said Ms Chilunda.

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EARC Field Day topic: Breeding, Genetics and New Varieties of Durum and Spring Wheat - Sidney Herald Leader

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'Diagnostic shock': the impact of results from ultrarapid genomic sequencing of critically unwell children on aspects of family functioning | European...

image:Rodolphe Barrangou and Echo Pan manipulate good bacteria using CRISPR systems. view more

Credit: Marc Hall, NC State University

New North Carolina State University research shows progress in gathering information on an important yet difficult to characterize human gut bacterium called Bifidobacterium, which is used in many probiotics that help maintain healthy microbiomes. The findings hold promise to help make so-called good bacteria even better.

As our lab expands and diversifies the types of good bacteria that we work with, we turn to more finicky bacteria, like Bifidobacterium, said Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor of Food, Bioprocessing and Nutrition Sciences at NC State and corresponding author of a paper describing the research published today in Proceedings of the National Academy of Sciences. This bacterium is harder to grow and harder to work with than others, but we were able to make some important discoveries and understand more about the bacteriums genetic basis for its health-promoting functionalities.

Bifidobacterium is one of the two main players in the probiotic industry along with Lactobacillus and is particularly dominant in the colon of infants, said Meichen (Echo) Pan, an NC State Ph.D. student and first author of the paper. But it is much more difficult to manipulate compared to Lactobacillus.

NC State researchers used both the bacteriums internal CRISPR-Cas system as well as a portable engineered CRISPR effector to make their findings. CRISPR-Cas systems are adaptive immune systems that allow bacteria to withstand attacks from enemies like viruses. These systems have been adapted by scientists to remove or cut and replace specific genetic code sequences.

Bifidobacterium, it turns out, has an abundance of native CRISPR-Cas systems, and one of them is a relatively understudied type I-G system.

In separate experiments, the researchers used this internal system and a portable Cas effector called a cytosine base editor to resensitize a Bifidobacterium strain to a common antibiotic tetracycline. Many bacteria carry natural resistance to antibiotics.

Restoring antibiotic sensitivity is conceptually and practically important because bacteria can potentially transfer antibacterial resistance to other bacteria in the gut, Pan said.

The researchers also found tiny changes in different strains of the bacterium, so-called single nucleotide polymorphisms or SNPs, that seemed to reflect large differences in the phenotypes, or characteristics, of the strains.

This was a surprising lesson: One letter difference in strains with genetic codes that are over 99% similar can make huge differences, Barrangou said. What genes turn on and how they behave due to their environment can make a huge difference and will require researchers to customize the CRISPR tool to adapt the editing strategy accordingly.

NC State and the North Carolina Agricultural Foundation supported the work, in a collaborative effort with IFF. Co-authors of the paper include former NC State post-doctoral researcher Claudio Hidalgo-Cantabrana, NC State graduate student Avery Roberts, and former NC State staff scientist Yong Jun Goh, Wesley Morovic of IFF Health and Biosciences, and Kimberly K.O. Walden at the University of Illinois Urbana Champaign.

-kulikowski-

Note to editors: An abstract of the paper follows. Genomic and Epigenetic Landscapes Drive CRISPR-based Genome Editing in BifidobacteriumAuthors: Meichen Pan, Claudio Hidalgo-Cantabrana, Avery Roberts, Yong Jun Goh, Rodolphe Barrangou, NC State University; Wesley Morovic, IFF Health and Biosciences; Kimberly K.O. Walden, University of Illinois Urbana Champaign

Published: July 18, 2022 in Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2205068119

Abstract: Bifidobacterium is a commensal bacterial genus ubiquitous in the human gastrointestinal tract, which is associated with a range of health benefits. The advent of CRISPR-based genome editing technologies provides opportunities to investigate the genetics of important bacteria, and transcend the lack of genetic tools in bifidobacteria to study the basis for their health-promoting attributes. Here, we repurpose the endogenous type I-G CRISPR-Cas system and adopt an exogenous CRISPR base editor for genome engineering in B. animalis subsp. lactis, demonstrating that both genomic and epigenetic contexts drive editing outcomes across strains. We reprogrammed the endogenous type I-G system to screen for naturally occurring large deletions up to 27 kb, and to generate a 500 bp deletion in tetW to abolish tetracycline resistance. A CRISPR-cytosine base editor was optimized to install CG-to-TA amber mutations to re-sensitize multiple B. lactis strains to tetracycline. Remarkably, we uncovered new epigenetic patterns that are distributed unevenly among B. lactis strains, despite their genomic homogeneity, that may contribute to editing efficiency variability. Insights were also expanded to Bifidobacterium longum subsp. infantis to emphasize the broad relevance of these findings. This study highlights the need to develop individualized CRISPR-based genome engineering approaches for distinct bacterial strains and opens new avenues for engineering of next generation probiotics.

Proceedings of the National Academy of Sciences

Experimental study

Cells

Genomic and Epigenetic Landscapes Drive CRISPR-based Genome Editing in Bifidobacterium

18-Jul-2022

R.B., C.H.-C. and Y.J.G are inventors on several patents related to CRISPR-Cas systems and their uses. R.B. is a cofounder of Intellia Therapeutics, Locus Biosciences, TreeCo, CRISPR Biotechnologies and Ancilia Biosciences, and a shareholder of Caribou Biosciences, Inari Ag, Felix Biotechnologies, and Provaxus.C.H.-C. is a cofounder of Microviable Therapeutics and shareholder of CRISPR Biotechnologies. W.M. is employed by IFF Health & Biosciences, International Flavors and Fragrances, Inc., which commercializes probiotic products.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Researchers lift the veil on stubborn probiot - EurekAlert

Scientists in Dubai have identified genetic factors that may put certain children at greater risk of having a potentially fatal reaction when infected with Covid-19.

Researchers used data from dozens of youngsters in Dubai and Jordan to determine what genetic variants increased the likelihood of them developing multisystem inflammatory syndrome in children (MIS-C).

Previous studies have highlighted the role genes play in causing MIS-C, but this new research is unusual in that it included many Arab children, who are often not included in large numbers in studies of this kind.

The work was led by scientists at Mohammed Bin Rashid University of Medicine and Health Sciences and Al Jalila Childrens Hospital, both in Dubai, and published in JAMA Network Open.

This is an important study not only because the findings show comprehensive genetic profiling of children with MIS-C, which is essential to characterise the genetic contribution to the disease, but also because patients of an Arab background have long been under-represented in genetic studies, Dr Walid Abuhammour, head of the paediatric infectious diseases department at Al Jalila Childrens Specialty Hospital, and study investigator, said.

In the US, children under 5 can now receive the Pfizer vaccine. AP

The study involved analysing the genes, clinical symptoms and other factors of 45 Arab and Asian children who developed MIS-C, and comparing them to 25 children who also had Covid-19 but did not develop MIS-C.

The children were treated at Al Jalila Childrens Specialty Hospital and the Jordan University Hospital between September 2020 and August 2021.

MIS-C involves a type of over-reaction of the immune system, known as a cytokine storm, that can affect multiple organs and result in death. The cytokine storm has also been associated with deaths from Covid-19 in adults.

Among the other institutions to have researched MIS-C is Boston Childrens Hospital, which released a study in September that identified genetic risk factors that all pointed to, the hospital said, underlying problems with immune regulation.

These variants caused the children to have what was described as an exaggerated response to viral infections, something that before the coronavirus emerged actually helped these individuals fight off infections. Particular chemical messengers in the body that stimulate the immune system were blamed for the over-reaction associated with MIS-C, as they could cause inflammation if released at the wrong time.

Like the Boston study last year, and others, the new research found that children who developed MIS-C were more likely to have particular rare genetic variants linked to the immune system.

Although clinical presentations and laboratory markers in this cohort were consistent with recently described MIS-C cohorts elsewhere, our analysis revealed significant enrichment of rare, likely deleterious [harmful] [genetic] variants, the study said.

These variants affect particular biochemical processes, the paper stated, that overlap with the currently characterised immunologic profile in patients with MIS-C.

The onset of the disease and resistance to treatment were also associated with genetic factors identified by the scientists.

The results of this research suggest that rare genetic factors play a role in MIS-C disease and highlight immune-related pathways which might become targets for intervention, Dr Ahmad Abou Tayoun, director of Al Jalila Children's Genomics Centre and associate professor of genetics at MBRU, said.

Hopefully, this will now prompt additional studies to functionally characterise some of the identified genes, and to expand genomic sequencing to more diverse populations to fully characterise the genetic landscape of this new disease entity.

The research was funded by the Al Jalila Foundation, which was founded by Sheikh Mohammed bin Rashid, Vice President and Ruler of Dubai.

As well as researchers at MBRU and Al Jalila Childrens Hospital, the study involved scientists at Dubai Health Authority, the University of Jordan and The Specialty Hospital in Amman.

Updated: July 10, 2022, 5:03 AM

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Rare study involving Arab children finds genetic factors linked to severe Covid-19 illness - The National