Category Archives: Genetics

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."

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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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Embrace technology to treat people according their genetics, call - The Citizen

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United States of AmericaUS Virgin IslandsUnited States Minor Outlying IslandsCanadaMexico, United Mexican StatesBahamas, Commonwealth of theCuba, Republic ofDominican RepublicHaiti, Republic ofJamaicaAfghanistanAlbania, People's Socialist Republic ofAlgeria, People's Democratic Republic ofAmerican SamoaAndorra, Principality ofAngola, Republic ofAnguillaAntarctica (the territory South of 60 deg S)Antigua and BarbudaArgentina, Argentine RepublicArmeniaArubaAustralia, Commonwealth ofAustria, Republic ofAzerbaijan, Republic ofBahrain, Kingdom ofBangladesh, People's Republic ofBarbadosBelarusBelgium, Kingdom ofBelizeBenin, People's Republic ofBermudaBhutan, Kingdom ofBolivia, Republic ofBosnia and HerzegovinaBotswana, Republic ofBouvet Island (Bouvetoya)Brazil, Federative Republic ofBritish Indian Ocean Territory (Chagos Archipelago)British Virgin IslandsBrunei DarussalamBulgaria, People's Republic ofBurkina FasoBurundi, Republic ofCambodia, Kingdom ofCameroon, United Republic ofCape Verde, Republic ofCayman IslandsCentral African RepublicChad, Republic ofChile, Republic ofChina, People's Republic ofChristmas IslandCocos (Keeling) IslandsColombia, Republic ofComoros, Union of theCongo, Democratic Republic ofCongo, People's Republic ofCook IslandsCosta Rica, Republic ofCote D'Ivoire, Ivory Coast, Republic of theCyprus, Republic ofCzech RepublicDenmark, Kingdom ofDjibouti, Republic ofDominica, Commonwealth ofEcuador, Republic ofEgypt, Arab Republic ofEl Salvador, Republic ofEquatorial Guinea, Republic ofEritreaEstoniaEthiopiaFaeroe IslandsFalkland Islands (Malvinas)Fiji, Republic of the Fiji IslandsFinland, Republic ofFrance, French RepublicFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabon, Gabonese RepublicGambia, Republic of theGeorgiaGermanyGhana, Republic ofGibraltarGreece, Hellenic RepublicGreenlandGrenadaGuadaloupeGuamGuatemala, Republic ofGuinea, RevolutionaryPeople's Rep'c ofGuinea-Bissau, Republic ofGuyana, Republic ofHeard and McDonald IslandsHoly See (Vatican City State)Honduras, Republic ofHong Kong, Special Administrative Region of ChinaHrvatska (Croatia)Hungary, Hungarian People's RepublicIceland, Republic ofIndia, Republic ofIndonesia, Republic ofIran, Islamic Republic ofIraq, Republic ofIrelandIsrael, State ofItaly, Italian RepublicJapanJordan, Hashemite Kingdom ofKazakhstan, Republic ofKenya, Republic ofKiribati, Republic ofKorea, Democratic People's Republic ofKorea, Republic ofKuwait, State ofKyrgyz RepublicLao People's Democratic RepublicLatviaLebanon, Lebanese RepublicLesotho, Kingdom ofLiberia, Republic ofLibyan Arab JamahiriyaLiechtenstein, Principality ofLithuaniaLuxembourg, Grand Duchy ofMacao, Special Administrative Region of ChinaMacedonia, the former Yugoslav Republic ofMadagascar, Republic ofMalawi, Republic ofMalaysiaMaldives, Republic ofMali, Republic ofMalta, Republic ofMarshall IslandsMartiniqueMauritania, Islamic Republic ofMauritiusMayotteMicronesia, Federated States ofMoldova, Republic ofMonaco, Principality ofMongolia, Mongolian People's RepublicMontserratMorocco, Kingdom ofMozambique, People's Republic ofMyanmarNamibiaNauru, Republic ofNepal, Kingdom ofNetherlands AntillesNetherlands, Kingdom of theNew CaledoniaNew ZealandNicaragua, Republic ofNiger, Republic of theNigeria, Federal Republic ofNiue, Republic ofNorfolk IslandNorthern Mariana IslandsNorway, Kingdom ofOman, Sultanate ofPakistan, Islamic Republic ofPalauPalestinian Territory, OccupiedPanama, Republic ofPapua New GuineaParaguay, Republic ofPeru, Republic ofPhilippines, Republic of thePitcairn IslandPoland, Polish People's RepublicPortugal, Portuguese RepublicPuerto RicoQatar, State ofReunionRomania, Socialist Republic ofRussian FederationRwanda, Rwandese RepublicSamoa, Independent State ofSan Marino, Republic ofSao Tome and Principe, Democratic Republic ofSaudi Arabia, Kingdom ofSenegal, Republic ofSerbia and MontenegroSeychelles, Republic ofSierra Leone, Republic ofSingapore, Republic ofSlovakia (Slovak Republic)SloveniaSolomon IslandsSomalia, Somali RepublicSouth Africa, Republic ofSouth Georgia and the South Sandwich IslandsSpain, Spanish StateSri Lanka, Democratic Socialist Republic ofSt. HelenaSt. Kitts and NevisSt. LuciaSt. Pierre and MiquelonSt. Vincent and the GrenadinesSudan, Democratic Republic of theSuriname, Republic ofSvalbard & Jan Mayen IslandsSwaziland, Kingdom ofSweden, Kingdom ofSwitzerland, Swiss ConfederationSyrian Arab RepublicTaiwan, Province of ChinaTajikistanTanzania, United Republic ofThailand, Kingdom ofTimor-Leste, Democratic Republic ofTogo, Togolese RepublicTokelau (Tokelau Islands)Tonga, Kingdom ofTrinidad and Tobago, Republic ofTunisia, Republic ofTurkey, Republic ofTurkmenistanTurks and Caicos IslandsTuvaluUganda, Republic ofUkraineUnited Arab EmiratesUnited Kingdom of Great Britain & N. IrelandUruguay, Eastern Republic ofUzbekistanVanuatuVenezuela, Bolivarian Republic ofViet Nam, Socialist Republic ofWallis and Futuna IslandsWestern SaharaYemenZambia, Republic ofZimbabwe

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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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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.

Read more:
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

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

YOUNG red meat industry stakeholders were told to treat tradition as an opportunity, during the 2022 Intercollegiate Meat Judging Association Conference in New South Wales last week.

At Charles Sturt Universitys Wagga Wagga campus, NSW prime lamb seedstock producer Tom Bull described how he moved on from industry tradition to succeed. He said the sheep industry in the 1990s was subjective: The show was king.

Tom Bull addressing the ICMJ conference in Wagga this week

The key for most breeders was trying to win a bit of felt and the whole industry was trying to win this bit of felt at a show and thats how it went.

It was all purebred, very wool-focused, lamb was a by-product and at that time lamb was declining in popularity, it was too fat, eye muscles were too small and consumption per capita was really declining.

Mr Bull said one of the most influential people on his career was a former Inghams Chicken employee who explained how the Inghams business was based on producing a meal for two at two different price points.

And then they would work back and find out what genetics and what feed they would need. Everything we have done since is trying to do that, he said.

He said he look at the sheep stud industry and thought: The best thing about the stud industry is they wont change. They are still going to show sheep, the average stud breeder is about 70 years of age, he said.

So then all of a sudden, really our business was based about looking at opportunities.

The first was use of objective data, performance recording data, he said.

We were one of the first people in Lambplan in 1994 and using data, and that was not the done thing, its all about the eye, 50 years trying to train your eye how to pick a sheep.

The other one that really came up was to use composite sheep, again not the done thing purebred sheep, you cant taint the breed, you cant register them with your breed society, he said.

Mr Bull said he applied Apple thinking people dont know what they need, I didnt know I needed an iPhone.

It was really that Apple thinking, trying to think ahead, trying to work out what people need and I think thats really where our opportunities (are) performance recording, self-replacing flocks.

You could see the whole Australian lamb industry was based on Merino sheep, because we were wool-focused, wool is king, he said.

So really all we tried to do was go, why not have specialist meat flocks? We used to say, why not have the Angus cow of the Australian lamb industry.

Mr Bull said seven breeds were put together to develop the Primeline Maternal.

Every agent, every buyer was saying No, you cant do that. Within five years we broke the Australian ram sales record selling composite rams, and as lambs, half the age of the other fellows, he said.

So I think when I look at the industry, tradition is what got me ahead.

As young people, see that as an opportunity, dont see that as a threat, he said. The tradition of the industry is what enabled us to actually grow.

Mr Bull said the beef sector had applied IBISWorld founder Phil Ruthvens message at a Holbrook Meat Profit day in 2000 that the meat industry needed to become a wine industry.

You need provenance, you need point of difference. What actually happened we saw the beef industry take that up brands emerged, certified Angus beef, the Wagyu juggernaut was just starting to roll and then you look at whats happened since that time, he said.

The whole (southern) industrys been painted black based on one thing eating quality.

The beef industry is about brands now.

His favourite beef brand is Rangers Valley WX5. I know how it will eat it eats the same every time.

But Mr Bull said lamb is still just lamb.

Were where beef was 20-something years ago, but lamb is just lamb, there is no point of difference, some eats good, some eats bad. But what do you reckon my next opportunity is? Eating quality.

Mr Bull said looking at intramuscular fat, with an Australian average of 4.2pc,

The 46 year-old Lampro principal who said he still thinks he is 20, advised his audience to use their time wisely.

One minute you are thinking, you know, worrying about bar night and the next minutes youve got kids and farms and everything else.

His first job after his University of Sydney degree was working in the boning room of an American company Superior Farms trying to substitute US lamb with Australian product.

It was great because I actually understood about meat, it was probably one of the best things I ever did.

After Superior Farms left Australia, he stayed in the processing sector and was involved with the Viascan technology that measured the meat yield of carcases. He eventually became the marketing manager for Australia and New Zealand.

As it happened, New Zealand took it up and Australia to a limited degree.

He then headed home and briefly had a business processing his own wool into doonas, eventually marketing them nationwide through Grace Bros. (now Myers).

It was really good experience, learnt a lot, lost a lot of money, learned a lot about Underbelly One because all the people I had to deal with I felt were Mafia in Melbourne.

Mr Bull said he started Lambpro with five stud ewes in 1991 and now ran 10,500 sheep and will sell 400 rams this year.

And 1.1 million or nearly 5 percent of Australias lambs are now sired by our rams that come off our farm.

See more here:
Apply 'Apple thinking' to genetic selection, ICMJ conference students told - Beef Central

Millions of people waiting for hip and knee surgery could soon be told whether their operation is likely to fail after scientists discovered a link between genetics and early failure of joint replacements.

In a world first, British researchers have found that DNA signals in saliva and blood samples are linked to an adverse reaction to the cobalt chrome materials in most joint implants.

It is thought a test to identify those patients who will have an adverse reaction to cobalt chrome will take at least two years before it can be rolled out but once in place should reduce the number of failed operations drastically.

About 15 per cent of Britons have these genetic characteristics, which make the immune system attack tissue around the material, causing pain and swelling, in a process similar to how a patient rejects an organ transplant.

Until now experts did not know what was causing the problem, which meant doctors had no way of telling if a patient would react badly to their new joint or not.

The research could lead to patients having more choice about what type of joint implant they decide on to boost their chance of success, which would transform the way orthopaedic surgery is carried out around the world.

In a trial, more than 600 patients who underwent joint-replacement surgery in the past 10 years were tested using saliva swabs and blood tests.

A computer analysed the data and revealed those patients who suffered complications carried specific genes. The team believe they can use this testing system to spot who would be at risk.

Currently, around 10 per cent of the population in the UK will have a joint surgically replaced in their lifetime, as a proven way to treat joint ailments such as arthritis. But as populations around the world grow older and heavier, this is leading to more joint replacement being performed, with some five million surgeries carried out across the world each year a number which is forecast to double over the next two decades.

The majority of patients are satisfied with the results of their surgery if joint replacements are successful they last between 15 and 25 years but a significant number of joint replacements fail early following adverse immune responses, leading to potentially dangerous and costly repeat surgery.

Patients with a genetic sensitivity to cobalt chrome usually have a second procedure within months of the first, using alternative materials.

The international study led by Newcastle University and published in Nature Communications Medicine, is the culmination of 14 years research by Dr David Langton, managing director at ExplantLab, a Newcastle-based organisation that investigates the links between genetics and the performance of medical devices which took part in the study.

Dr Langton said: Through our research we have been able to demonstrate that a significant percentage of patients carry a genotype that makes it more likely for them to have a reaction to a joint replacement made of a cobalt chrome component.

Our findings are a big step towards offering patients more choice about what type of joint implant they decide on, and helping them to make informed decisions about the risks involved.

Of the 6.4 million people currently on the waiting list for treatment on the NHS in England, more than 730,000 require orthopaedic surgery. Cobalt chrome is used in over 95 per cent of knee replacements, but alloys such as titanium and ceramic metals can be used as alternative, according to surgeons.

Tony Nargol, consultant orthopaedic surgeon at North Tees and Hartlepool NHS Foundation Trust, whose surgical team worked closely with Dr Langton, said: This exciting discovery comes as a result of the close working relationship our fantastic staff have had with Mr Langton and his team, as well as health staff from organisations across the world.

This work will help provide a practical way for health professionals to help patients in selecting the best type of implants for their individual bodies. It will mean better outcomes for our patients and could transform the quality of care we provide to our patients.

See more here:
Genetic test could tell millions of NHS patients if their hip or knee surgery will fail - iNews

In the modern age, lifestyle plays a very crucial role to keep us mentally and physically healthy and when it comes to mens health, we often talk about cholesterol, diabetes, hypertension, early onset heart attack, life expectancy and so on but when it comes to reproductive health, leading to infertility or reproductive losses, males seem to be less informed. Nowadays, there is a high rise of delayed marriages and couples opting for only one or two children as infertility is now a major concern for such couples.

In about 50% of such cases, infertility is attributable to the male partner, mainly due to a failure in spermatogenesis and according to several studies, a severe decline in the sperm quality has been observed mostly contributed by the lifestyle, including smoking, drinking, long driving hours, stress and pollution. In a study done by Levine H et al., 2017, it was reported that there is a decline of 5060% in sperm counts amongst men from North America, Europe, Australia and New Zealand.

It is important to understand the various factors which impact sperm quality as well as the male fertility. In an interview with HT Lifestyle, Upasana Mukherjee, Senior Genetic Counsellor at Neuberg Center for Genomic Medicine, shared The modern man, during his reproductive period, is exposed to the negative influence of widespread lifestyle-related habits such as smoking, alcohol, recreational drugs, less physical activity etc. Effect of cigarette smoking on male fertility may result from the combined roles of elevated oxidative stress, DNA damage, and cell apoptosis, which could explain not only the reduction in semen quality but also impaired spermatogenesis, sperm maturation, and sperm function reported to be present in smokers compared to non-smokers."

She added, "Smoking is not only associated with decreased sperm quality, it has also been found to be responsible for morphological changes of sperm and also with sperm DNA damage. The high sperm DNA fragmentation rate can contribute to male infertility and has also been associated with multiple miscarriages. It is found that the higher the sperm DNA damage index, the lesser the chances of achieving an ongoing pregnancy. Sperm DNA fragmentation analysis is now offered by many labs to assess the level of damaged sperms. This in turn can help the couple to take alternative reproductive methods (ART) for a successful pregnancy. Chronic alcohol consumption has also been found to have a detrimental effect on both semen quality and the levels of male reproductive hormones.

Gaur D.S et al.,2010 conducted a study on the male partners of couples facing primary infertility and they found that teratozoospermia (abnormal sperm morphology) was present in 63% and 72% of males who drank alcohol moderately (4080g/day) and heavily (>80g/day), respectively. None of the heavy alcohol drinkers were normozoospermic and most were oligozoospermic (64%), which is suggestive of progressive testicular damage in relation to increasing daily alcohol intake. Although the effects of alcohol on male reproductive function are dependent on the intake amount, a threshold amount of alcohol beyond which the risk of male infertility increases has not yet been determined. Several recreational drugs such as marijuana, cocaine, anabolicandrogenic steroids (AAS), opiates (narcotics) and methamphetamines are examples of illicit drugs that exert a negative impact on male fertility.

Upasana Mukherjee highlighted, About 15% of males with infertility have an underlying genetic cause. The genetic landscape of male infertility is highly complex, and at least 200 genes have been implicated in spermatogenesis. Over 25% azoospermic males have genetic causes. These include mostly chromosomal abnormalities (e.g sex chromosome abnormalities, Y chromosome microdeltion) involved in severe spermatogenic impairment and autosome-linked gene variations involved in central hypogonadism, monomorphic teratozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenic disturbances. Genetic testing is relevant for its diagnostic value, clinical decision making, and appropriate genetic counseling.

According to Dr Sheetal Sharda, Clinical Geneticist and Director- Genomics Development and Implementation, unlike women, men are less aware about their reproductive health and when it comes to being evaluated for infertility or pregnancy loss, often the female is evaluated first but pregnancy and a positive pregnancy outcome are both dependent on both the partners. She revealed, With better understanding and awareness, timely evaluation for a genetic diagnosis and making lifestyle modifications can improve the reproductive health of both the partners.

Excerpt from:
Men's health and infertility: Is it lifestyle or genetics? Experts answer - Hindustan Times