Distorted, stretched DNA may increase risk of off-target changes with CRISPR-Cas9

Phys.org | February 26, 2019

Distortions to DNA, which occur routinely during gene expression and other cellular processes, could lead to off-target changes to the genome when using CRISPR-Cas9, a new study suggests. The Medical Research Council scientists behind the research say that their findings may help to pave the way to improve on the accuracy of gene editing for clinical applications. During the expression of genes, DNA is stretched and distorted out of its usual shape. While this is needed for proper function of the cell's own machinery, it may pose a challenge for CRISPR-Cas9 gene editing by increasing the risk of off-target edits, potentially introducing harmful changes. The findings, from scientists at the MRC London Institute of Medical Sciences and AstraZeneca, are published today in the journal Nature Structural and Molecular Biology. CRISPR-Cas9, a gene editing tool that allows researchers to find and edit strands of DNA, has gained worldwide recognition for its multitude of purposes as scientists use the technology across a range of sectors, including medicine, drug discovery and agriculture.

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Naveris Inc. Raises $51 Million to Advance Commercialization of NavDx

Naveris, Inc. | September 20, 2022

Naveris, Inc., a commercial-stage life sciences company dedicated to improving patient care through earlier detection of viral-driven cancers, today announced a $33.4 million expansion of its Series A financing, bringing the total investment in Naveris to $51 million. The financing was led by Gurnet Point Capital, joined by TechU Ventures and BrightEdge, the impact and venture capital arm of the American Cancer Society. Naveris’ blood tests for earlier cancer detection use proprietary patented DNA fragmentomics technology to distinguish between viral DNA arising from cancers versus infection. Proceeds from this financing will be used to advance commercialization of NavDx, Naveris’ flagship blood test for the early detection of cancers caused by the human papillomavirus (HPV), and to generate the clinical data needed to expand into other cancer types and indications. “We are delighted to have the continued support of Gurnet Point Capital and TechU Ventures, and to welcome Alice Pomponio and the rest of the BrightEdge team, who collectively bring a deep understanding of both the oncology space and commercial-stage businesses. We founded Naveris on the belief that advances in molecular diagnostics will play a vital role in improving cancer outcomes. This new investment underscores NavDx’s commercial success and potential, and our experienced team’s ability to transform this vision into a reality for patients and oncologists.” Piyush B. Gupta, Ph.D., Naveris founder and Chief Executive Officer "Since our initial investment in 2020, we have been impressed by the Naveris team's vision and their ability to commercially execute on a differentiated strategy in the rapidly developing field of blood-based cancer detection,” said Travis Wilson, Partner at Gurnet Point Capital. “We are pleased to be providing additional capital to ensure that their transformative technology for early cancer detection will benefit as many patients as possible." “We could not be more excited to back Piyush and his team as Naveris works to increase access to diagnose, detect, and monitor viral cancers” said Alice Pomponio, BrightEdge Managing Director. “We understand the burden of HPV related cancers on patients. And we seek to build on the years of research and advocacy of the American Cancer Society to support the next generation of mission aligned companies reducing patient burden.” Along with Naveris' commercial activities, more than 25 medical institutions have partnered with the company to conduct clinical studies and trials utilizing its technology. The company has also partnered with biotechnology companies developing immunotherapies for HPV-related cancers. About Naveris, Inc. Founded in 2017, Naveris is a privately held biotechnology company with facilities in Massachusetts and North Carolina. The company’s mission is to improve outcomes for the millions of people at risk of developing viral cancers through novel molecular diagnostics that enable earlier cancer detection. Naveris’ clinical laboratory is certified for high complexity testing under CLIA, and is accredited by the College of American Pathologists and the New York State Department of Health Wadsworth Center. About Gurnet Point Capital Gurnet Point Capital is a leading healthcare fund that invests in de-risked life sciences companies. Gurnet Point primarily focuses on businesses that have high growth potential in the late product development and commercialization stages of their evolution. These companies become partners not just because of their capacity to generate economic value, but also because of their potential to deliver social impact. Gurnet Point’s team of highly experienced industry executives work closely with its portfolio companies, with an active approach driving operational transformation and outsized returns.

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CELL AND GENE THERAPY

Adicet Bio Reports Inducement Grants under Nasdaq Listing Rule 5635(c)(4)

Adicet Bio, Inc. | September 06, 2022

Adicet Bio, Inc. a clinical-stage biotechnology company discovering and developing allogeneic gamma delta CAR T cell therapies for cancer, today announced it granted inducement awards on August 31, 2022 under Adicet’s 2022 Inducement Plan as a material inducement to employment to five individuals hired by Adicet in August 2022. The employees received, in the aggregate, non-qualified stock options to purchase 114,200 shares of Adicet’s common stock with an exercise price of $14.16 per share, the closing price of Adicet’s common stock as reported by Nasdaq on August 31, 2022. One-fourth of the shares underlying each employee’s option will vest on the one-year anniversary of each recipient’s start date and thereafter the remaining three-fourths of the shares underlying each employee’s option will vest in thirty-six substantially equal monthly installments, such that the shares underlying the option granted to each employee will be fully vested on the fourth anniversary of the recipient’s start date, in each case, subject to each such employee’s continued employment with Adicet on such vesting dates. All of the above-described awards were granted outside of Adicet’s stockholder-approved equity incentive plans pursuant to Adicet’s 2022 Inducement Plan, which was adopted by the board of directors in January 2022. The awards were authorized by the compensation committee of the board of directors, which is comprised solely of independent directors, as a material inducement to the employees entering into employment with Adicet in accordance with Nasdaq Listing Rule 5635(c)(4). About Adicet Bio, Inc. Adicet Bio, Inc. is a clinical-stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors and T cell receptor-like antibodies to enhance selective tumor targeting, facilitate innate and adaptive anti-tumor immune response, and improve persistence for durable activity in patients.

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CELL AND GENE THERAPY

Rocket Pharmaceuticals to Acquire Renovacor, Extending Leadership in AAV-based Cardiac Gene Therapy

Rocket Pharmaceuticals, Inc. | September 21, 2022

Rocket Pharmaceuticals, Inc. a leading late-stage, clinical biotechnology company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders with high unmet need, and Renovacor, Inc. a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases, today announced a definitive agreement under which Rocket will acquire Renovacor in an all-stock transaction for an implied value of approximately $2.60 per share, based on the volume weighted average trading price of Rocket shares of $15.51 for the 30 trading days through and including Monday, September 19, 2022. The boards of directors of both companies have unanimously approved the transaction, which is currently expected to close by the first quarter of 2023. “The acquisition of Renovacor aligns with our strategy to expand our leadership position in AAV-based gene therapy for cardiac disease and gives us a perfect opportunity to continue on our mission to transform the lives of heart failure patients through the power of gene therapy. Building on our success in Danon Disease to date, I am particularly excited to expand our cardiology focus and capabilities and address a clear unmet medical need in BAG3-associated dilated cardiomyopathy. By combining Renovacor’s compelling preclinical work with our joint clinical, regulatory and CMC expertise, we believe we will be well-positioned to bring the highest impact gene therapy with the best chance for success to these patients in the most productive and efficient manner possible.” Gaurav Shah, M.D., Chief Executive Officer of Rocket Dr. Shah continued, “Given the positive pediatric safety data previously announced from our Phase 1 RP-A501 Danon Disease program, and the upcoming pediatric efficacy data and longer-term adult cohort data we anticipate presenting at the Heart Failure Society of America (HFSA) Scientific Meeting at the end of this month, this strategic acquisition gives us what we believe is the broadest platform in the field to address these devastating rare cardiac diseases. Furthermore, the acquisition will bring to Rocket key personnel, namely a team of leading cardiology drug development experts, critical capabilities, and valuable IP to support continued development of the BAG3 as well as other potential cardiac programs, including a gene therapy research collaboration for arrhythmogenic cardiomyopathy.” Renovacor’s most advanced program, REN-001, is an AAV-based gene therapy targeting BAG3-associated dilated cardiomyopathy (DCM), a severe form of heart failure. BAG3-DCM represents a significant unmet medical need in a patient population with rapidly progressive cardiac dysfunction in whom no treatments targeting the underlying mechanism of disease exist. Renovacor has deep technical expertise in the development of precision therapies that address genetically driven cardiac diseases. Further, Renovacor is supported by world-class scientific collaborators, a robust intellectual property portfolio and personnel with expertise in BAG3-DCM. These assets and capabilities, all together, represent tremendous value and will enhance Rocket’s leading position in cardiac AAV-based gene therapy. “Renovacor has made tremendous progress in advancing targeted gene therapies to address the high unmet medical needs of patients living with genetically driven forms of heart disease,” said Magdalene Cook, MD, Chief Executive Officer of Renovacor. “Our experienced team is excited to join Rocket in a shared vision of broadening patient access to precision medicines for cardiovascular disease and addressing common barriers jointly. We look forward to combining the considerable resources and expertise of Renovacor and Rocket in creating a category leader in the precision cardiology field. As a result of this combination, we will be suspending current guidance regarding preclinical and clinical timelines for our programs as we evaluate these items with the Rocket team.” It is currently anticipated that the transaction will close by the first quarter of 2023, subject to approval by Renovacor and Rocket shareholders, receipt of any required customary regulatory approvals and the satisfaction of other customary closing conditions. RTW Investments, LP, a significant shareholder of both Rocket and Renovacor, has entered into a voting agreement with Renovacor, pursuant to which they have agreed, among other things, and subject to the terms and conditions of the agreement, to vote in favor of the Renovacor acquisition as a Rocket stockholder. SVB Securities is serving as exclusive financial advisor and Goodwin Procter LLP is serving as legal counsel to Rocket. Wells Fargo Securities is serving as exclusive financial advisor and Troutman Pepper Hamilton Sanders LLP is serving as legal counsel to Renovacor. About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The Company’s platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rocket’s first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon Disease, a devastating, pediatric heart failure condition. About Renovacor Renovacor is a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases. The company’s lead program in BAG3-associated dilated cardiomyopathy (DCM) uses gene transfer technology to address the monogenic cause of this severe form of heart failure. Renovacor’s vision is to bring life-changing therapies to patients living with serious genetic cardiovascular and related diseases, by developing medicines that target the underlying cause of disease and provide a transformative benefit and significant improvement to quality of life.

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