A new CRISPR/Cas9 therapy can suppress aging

Medical Xpress | February 19, 2019

Aging is a leading risk factor for a number of debilitating conditions, including heart disease, cancer, and Alzheimer's disease, to name a few. This makes the need for anti-aging therapies all the more urgent. Now, Salk Institute researchers have developed a new gene therapy to help decelerate the aging process. The findings, published on February 18, 2019, in the journal Nature Medicine, highlight a novel CRISPR/Cas9 genome-editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans. This treatment provides important insight into the molecular pathways involved in accelerated aging, as well as how to reduce toxic proteins via gene therapy. "Aging is a complex process in which cells start to lose their functionality, so it is critical for us to find effective ways to study the molecular drivers of aging," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and senior author of the paper. "Progeria is an ideal aging model because it allows us to devise an intervention, refine it and test it again quickly."

Spotlight

Phenylmethylsulfonyl fluoride, better known as PMSF, is a small molecule serine protease inhibitor used to prevent unwanted proteolysis. 

Spotlight

Phenylmethylsulfonyl fluoride, better known as PMSF, is a small molecule serine protease inhibitor used to prevent unwanted proteolysis. 

Related News

INDUSTRIAL IMPACT, DIAGNOSTICS

Vaxxinity Announces First Subjects Dosed in Phase 1 Clinical Trial of VXX-401, Investigational Anti-PCSK9 Vaccine to Treat Hypercholesterolemia

Vaxxinity, Inc. | March 21, 2023

Vaxxinity, Inc. a U.S. company pioneering the development of a new class of immunotherapeutic vaccines, announced that the first subjects have been dosed in a randomized, double-blind, placebo-controlled Phase 1 clinical trial of VXX-401, an investigational vaccine designed to lower low-density lipoprotein (LDL) cholesterol, a known factor contributing to heart disease, by targeting proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9). Heart disease remains the leading cause of death globally, claiming over 18 million lives per year, despite the existence of approved treatments that lower LDL. “This is an exciting milestone for VXX-401 and Vaxxinity in our pursuit to vaccinate the world against heart disease with a preventative option that is convenient and accessible, addressing an unmet need to combat the leading global cause of death,” said Mei Mei Hu, Chief Executive Officer of Vaxxinity. “PCSK9 antibody therapies are well-tolerated and effective, but huge unmet patient need remains. In order to solve the problem of heart disease, the world needs a scalable, accessible technology that can reach the hundreds of millions, if not billions of people at risk. With an LDL-lowering vaccine we can potentially offer an option that’s cost-effective, safe, convenient, long-acting, and deployable.” The multicenter Phase 1 dose-escalation trial aims to enroll 48 subjects aged 18 to 75 years, with LDL cholesterol between 2.59 and 4.89 mmol/L. The objectives of the trial are to evaluate safety, tolerability and immunogenicity (as measured by serum anti-PCSK9 antibody titers). Pharmacodynamics of the immune response will be measured by LDL cholesterol levels, an established model of PCSK9 inhibition in hypercholesterolemia. “We’re excited to get this first-in-human trial of VXX-401 started. The concept of a vaccine for cholesterol could be a game-changer in cardiovascular health due to its potentially very broad reach and impact on human health,” said Professor Stephen Nicholls of Monash University and Victorian Heart Hospital in Australia. “Targeting PCSK9 with a monoclonal antibody is a proven and effective approach for lowering cholesterol and reducing the risk of heart attack and stroke. Despite the availability of statins and the approval of PCSK9-targeting medicines, there is still a need for new therapies. VXX-401 has the potential to extend the use of PCSK9 inhibition to the full population who could benefit.” Earlier this month, Vaxxinity presented pre-clinical data at the American College of Cardiology/World Congress of Cardiology Annual Scientific Session demonstrating that VXX-401 induced robust anti-PCSK9 antibodies and durable LDL cholesterol lowering without affecting high-density lipoprotein (HDL) cholesterol levels, indicating that VXX-401 has the potential to be a safe and effective LDL lowering therapy. Data in non-human primate studies show that VXX-401 was well tolerated and provided durable and significant LDL reduction of 30% to 50% change from baseline. The data also demonstrate VXX-401’s immunogenicity: purified antibodies from immunized animals bound to human PCSK9 with high affinity, and exhibited a dose-dependent functional inhibition of PCSK9 in vitro. Additionally, Peripheral Blood Mononuclear Cells (PBMCs) collected prior to immunization did not release cytokines upon stimulation with various components of the vaccine, suggesting that VXX-401 may safely overcome immune tolerance. About VXX-401 VXX-401 was designed using Vaxxinity’s proprietary synthetic peptide vaccine platform and is being developed for the treatment of hypercholesterolemia. The platform is designed to harness the immune system to convert the body into its own natural “drug factory,” stimulating the production of antibodies. VXX-401 is designed to induce robust, long-acting antibodies against PCSK9 in order to lower LDL cholesterol. About Vaxxinity Vaxxinity, Inc. is a purpose-driven biotechnology company committed to democratizing healthcare across the globe. The company is pioneering a new class of synthetic, peptide-based immunotherapeutic vaccines aimed at disrupting the existing treatment paradigm for chronic disease, increasingly dominated by monoclonal antibodies, which suffer from prohibitive costs and cumbersome administration. The company’s proprietary technology platform has enabled the innovation of novel pipeline candidates designed to bring the efficiency of vaccines to the treatment of chronic diseases, including Alzheimer’s, Parkinson’s, migraine, and hypercholesterolemia. The technology is also implemented as part of a COVID-19 vaccine program. Vaxxinity has optimized its pipeline to achieve a potentially historic, global impact on human health.

Read More

INDUSTRIAL IMPACT, MEDICAL

Synthego Introduces CRISPR Discovery Partners to Streamline CRISPR-Driven Drug Discovery Research

Synthego | March 17, 2023

Synthego Corp., a leading genome engineering solutions provider, announced today the launch of its service partner ecosystem, CRISPR Discovery Partners, designed to accelerate drug discovery by providing a seamless research workflow from CRISPR editing to phenotypic data and downstream services. The ecosystem brings together high-value partners including Arctoris, BrainXell, Curia, PhenoVista, and Pluristyx to offer a coordinated solution for CRISPR-driven drug discovery. The CRISPR Discovery Partner ecosystem creates an integrated workflow starting with Synthego's CRISPR Engineered Cells through functional readouts, providing researchers with a faster, more efficient, and more reliable way to move their discoveries forward. Researchers can access the full range of genome engineering services through Synthego, as well as downstream services including small molecule screening, cell-based assays, high content imaging, iPSC differentiation, and multi-omics through partners. The result is a streamlined drug discovery process that can help accelerate the development of life-saving treatments. Synthego's CRISPR Discovery Partners include Arctoris, a tech-enabled drug discovery service company, combines wet lab automation and machine learning with a world-class team of experienced drug discovery researchers to enable the accelerated development of small molecule, biologics, and cell therapy assets. BrainXell provides differentiation services to generate high-purity, iPSC-derived human neurons, astrocytes, and microglia for research use with a focus on drug discovery. BrainXell also offers fibroblast reprogramming and select downstream assay services. Curia, a global contract research, development and manufacturing organization (CDMO), offers products and services from discovery through manufacturing to help customers transform R&D results into real-world impact. PhenoVista, a San Diego-based CRO, specializes in modern, human, cell-based in vitro assay development and analysis. Internationally recognized for developing and implementing both fully bespoke projects and pre-validated Ready-2-Go assay services, this award-winning research partner leverages high-content imaging to enable life scientists to accelerate their discovery of novel therapeutics and improve global health. Pluristyx offers expertise and tools to support and accelerate the development and commercialization of revolutionary therapeutics to treat serious human diseases by providing unique products, consulting, and contract services, including cell line expansion and banking. About Synthego Synthego is a genome engineering company that enables the acceleration of life science research and development in the pursuit of improved human health. The company leverages machine learning, automation, and gene editing to build platforms and products for science at scale. With its foundations in engineering disciplines, the company's platform technologies vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance basic research, target validation, and clinical trials. With its technologies cited in hundreds of peer-reviewed publications and utilized by thousands of commercial and academic researchers and therapeutic drug developers, Synthego is at the forefront of innovation enabling the next generation of medicines by delivering genome editing at an unprecedented scale.

Read More

CELL AND GENE THERAPY, INDUSTRIAL IMPACT

CBM, Stoic Bio and Nucleus Biologics Announce Strategic Alliance

The Center for Breakthrough Medicines | March 13, 2023

Nucleus Biologics and Stoic Bio have teamed up to form a supply agreement with the Center for Breakthrough Medicines (CBM), a contract development and manufacturing organization that aims to accelerate the development and manufacture of advanced therapies. Under the agreement, Nucleus Biologics will become CBM's selected supplier of cell culture media and other biological solutions, ensuring a consistent supply of this critical material with tighter quality control measures. Nucleus Biologics' approach to cell culture media, which sees it as a critical raw material that can drive desired attributes of cells crucial to the success of cell and gene therapy research, is complementary to CBM's focus on transparency, technology, and end-to-end solutions. By working together, they hope to expedite cell and gene therapy breakthroughs. In addition, CBM will be an early adopter of Stoic Bio's innovative family of point-of-use media makers, Krakatoa™, which allows scientists to manufacture their own media with 65% fewer CO2 emissions than conventional media. By demonstrating that developing and manufacturing lifesaving therapies doesn't have to come with a high environmental cost, CBM hopes to set an example for the industry. With over 2,200 cell and gene therapies in development, collaborations like this one are needed to speed up the process of getting these therapies to the clinic and ultimately approved. The CBM, Stoic Bio and Nucleus Biologics collaboration aim to create a unique service offering that introduces a paradigm shift in development and manufacturing, showing how technology and sustainability can converge to make better therapies sustainably. About The Center for Breakthrough Medicines The Center for Breakthrough Medicines (CBM) is a CDMO focused on accelerating the development and manufacture of advanced therapies to save lives. It offers end-to-end solutions such as process development, manufacturing, and quality control for cell and gene therapies, gene editing, and immunotherapies. In addition, CBM collaborates with pharmaceutical companies, academic institutions, and healthcare providers to make advanced therapies more accessible while ensuring compliance with regulatory standards. The company also prioritizes sustainability by implementing green initiatives and sustainable technology and strives to positively impact the communities it operates in.

Read More