How genes affect tobacco and alcohol use

Medical Xpress | February 21, 2019

The use of alcohol and tobacco is closely linked to several diseases and is a contributing factor in many deaths. A recent study using data from 1.2 million people has now been published in the journal Nature Genetics. Several research groups around the world are involved, among them a group from the Nord-Trøndelag Health Study (HUNT) and the K.G. Jebsen Center for Genetic Epidemiology. "We discovered several genes associated with increased use of alcohol and tobacco. We also looked at the correlation between these genes and the risk of developing various diseases and disorders," says Professor Kristian Hveem at the HUNT Research Centre. He is also the head of the Jebsen Center and one of the study's co-authors. The research groups discovered a total of 566 gene variants at 406 different sites in the human genetic material that can be linked to the use of alcohol or tobacco. One hundred fifty of these sites are linked to the use of both tobacco and alcohol.

Spotlight

The availability of technologies for the generation of induced pluripotent stem cells (iPSCs) from somatic cells, such as skin and blood cells, has allowed researchers to generate limitless pools of iPSCs retaining the genetic makeup of the somatic cells from which they were derived. Together, iPSCs and CRISPR-Cas9 systems provide researchers with effective in vitro tools for assessing gene function, disease modeling, and regenerative therapy.

Spotlight

The availability of technologies for the generation of induced pluripotent stem cells (iPSCs) from somatic cells, such as skin and blood cells, has allowed researchers to generate limitless pools of iPSCs retaining the genetic makeup of the somatic cells from which they were derived. Together, iPSCs and CRISPR-Cas9 systems provide researchers with effective in vitro tools for assessing gene function, disease modeling, and regenerative therapy.

Related News

INDUSTRIAL IMPACT

Adcentrx and AvantGen Enter a New Partnership with a Three-year, Multi-target Collaboration to Discover Antibodies for Novel Antibody-drug Conjugates

Adcentrx Therapeutics | February 15, 2022

Adcentrx Therapeutics a biotechnology company focused on accelerating breakthroughs in antibody drug conjugate ("ADC") therapeutic development, and AvantGen, a leader in the use of yeast display technology for human antibody discovery and optimization, announced today a three-year, multi-target partnership for the discovery of antibodies to be developed into novel ADC therapeutic candidates. Under the terms of the collaboration, Adcentrx will specify targets against which AvantGen will screen for novel antibodies using its yeast display system. Adcentrx will be responsible for engineering the antibodies into ADC therapeutic candidates and has worldwide development and commercialization rights. AvantGen will be eligible to receive milestone payments for achievement of certain development milestones. "We are excited to enter this new partnership with AvantGen to accelerate our ADC development efforts. What attracted us to AvantGen initially is how their yeast display technology and human antibody libraries mimic human diversity to yield high affinity and very specific antibodies. Through our ongoing collaboration, AvantGen has demonstrated its capabilities in rapidly discovering a diverse antibody repertoire with high developability against defined targets. A key objective at Adcentrx, through this collaboration and opportunistic licensing activities, is to identify the best antibodies which we can leverage to assemble a pipeline of next generation ADC therapeutics." Hui Li, Ph.D., President and CEO of Adcentrx "We are proud to partner with Adcentrx to help accelerate its ADC pipeline build with our robust human antibody discovery platform," said Xiaomin Fan, Ph.D., President and CEO of AvantGen. "The speed that Adcentrx is able to take lead antibody candidates to development stage with its ADC technology is truly remarkable. We believe that this new partnership will enable Adcentrx to develop the most promising next generation ADC therapeutics with our high-quality antibodies." About Adcentrx Therapeutics Adcentrx is a biotechnology company focused on accelerating breakthroughs in protein conjugate therapeutic development for cancer and other life-threatening diseases. By combining the targeting precision of biologics and the disease fighting power of small molecule payloads, Adcentrx strives to develop next generation targeted therapies for improving patient treatment options. About AvantGen AvantGen, Inc is a leader in the use of yeast display technology for antibody discovery and optimization. Founded by experts in the creation of antibody discovery and optimization platforms, AvantGen excels in the rapid generation of antibodies for therapeutic, diagnostic and research tool applications. The Company's platforms include a robust yeast display system, large natural human antibody database, fully human antibody libraries comprised of over 100 billion antibody clones displayed by yeast cells, NK cell engager technology, flow cytometry-based and other screening technologies, as well as novel methodologies for rabbit monoclonal antibody and VHH nanobody generation. These versatile platforms can be used to discover antibodies directed at specific disease targets, affinity mature existing antibodies to improve their binding properties and humanize antibodies to render non-human antibodies suitable for human therapeutic applications, as well as generate rabbit monoclonal antibodies for applications that need extremely high specificity, such as antibodies capable of distinguishing point mutations and post-translational modifications for IHC, and anti-idiotype antibodies for PK studies. AvantGen's partners include pharmaceutical, biotech, diagnostic and government entities, many of which are repeat customers.

Read More

CELL AND GENE THERAPY

Gritstone bio and CEPI Expand Vaccine Agreement to Tackle Omicron Variant

Gritstone bio | December 07, 2021

Gritstone bio, Inc. a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, and CEPI, the Coalition for Epidemic Preparedness Innovations, announced the expansion of their agreement in order to support the development of a self-amplifying mRNA vaccine designed to tackle the Omicron COVID-19 variant. CEPI will provide up to $5 million in additional funding to conduct a Phase 1 clinical trial of Gritstone’s Omicron vaccine candidate in South Africa, where a CEPI-funded clinical trial of Gritstone’s Beta variant COVID-19 vaccine is due to begin shortly. The SARS-CoV-2 T cell epitopes administered within Gritstone’s SAM COVID-19 vaccines are minimally impacted by mutations found within the Omicron variant, reinforcing the platform’s potential to address both Omicron and future variants of concern. CEPI is already funding up to $20.6 million to support preclinical studies, manufacturing process optimization, and a Phase 1 trial of Gritstone’s Beta variant vaccine candidate which will be initiated by South Africa’s University of the Witwatersrand in the coming weeks. The funding announced today will expand the Phase 1 trial to include additional arms to evaluate an Omicron-specific version of the vaccine. Gritstone has commenced manufacturing its SAM vaccine to specifically target the Omicron variant, and the Omicron arms of the Phase 1 trial are expected to begin in Q2 2022, subject to regulatory approval. The recently described Omicron variant, first identified in South Africa on November 9, 2021, was designated a variant of concern by the World Health Organization (WHO) on November 26, 2021. Early evidence suggests that Omicron carries an increased risk of re-infection, and sequence analysis has revealed many mutations in Spike, which may reduce clinical effectiveness of existing vaccines and/or therapeutic antibodies. Enabling equitable access CEPI is committed to global equitable access to COVID-19 vaccines so, through this agreement, CEPI and Gritstone have agreed that this Omicron vaccine candidate will be made available to the COVAX Facility for procurement and allocation, if it is proven to be safe and effective. The COVAX Facility aims to deliver equitable access to COVID-19 vaccines for all countries, at all levels of development, that wish to participate. “While key questions are yet to be answered about Omicron, its transmissibility, and its potential ability to evade our current vaccines, the stakes are too high to delay developing Omicron-specific vaccine candidates. Given the uncertainties, we must accelerate crucial R&D so vaccines are available to tackle Omicron as soon as possible – just in case we need them. There is no time to lose, so I’m pleased that within 10 days of Omicron being declared a Variant of Concern by the WHO, CEPI is expanding its partnership with Gritstone to support a new Omicron vaccine candidate which can be made globally accessible through COVAX.” Dr Richard Hatchett, CEO of CEPI “Our vaccine platforms are built on the premise that a best-in-class vaccine against a virus will drive strong neutralizing antibodies directed to surface antigens such as Spike, and strong cytotoxic T cell responses against other conserved viral antigens to eliminate virally infected cells. This broad immune response would, in principle, provide superior protection against a virus that is mutating its surface protein. Omicron is an example of a novel SARS-CoV-2 variant that may escape clinical protection conferred by vaccines that only afford narrow, Spike-specific immunity,” said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone. “Our SAM technology provides an innovative platform likely capable of delivering on the attractive concept of broad, durable immunity. We are thrilled to be quickly expanding our relationship with CEPI in our shared goal of finding new vaccine solutions to battle this deadly virus on a global scale and help prevent current and perhaps future COVID outbreaks.” Self-amplifying mRNA vaccines As with the mRNA-based COVID-19 vaccines that are now in global use, self-amplifying mRNA vaccines use the body’s own machinery to make antigenic protein itself rather than injecting the antigen directly into the body. However, in self-amplifying mRNA vaccines, viral RNA is adapted in a way that allows only the genetic sequence for a specific antigen to be expressed, while keeping the part of the RNA that allows it to produce multiple copies of itself—the self-amplification machinery. The benefit of this approach is that the dose of RNA can be reduced while maintaining the potency of the vaccine. Gritstone’s vaccine candidate may also elicit T-cell immune responses against non-Spike gene fragments, which are slower to mutate than the genes associated with the SARS-CoV-2 Spike protein and could potentially provide broad protection against other SARS-CoV-2 strains. About CEPI CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017, to develop vaccines against future epidemics. Prior to COVID-19 CEPI’s work focused on developing vaccines against Ebola virus, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever virus and Chikungunya virus – it has over 20 vaccine candidates against these pathogens in development. CEPI has also invested in new platform technologies for rapid vaccine development against unknown pathogens. During the current pandemic, CEPI initiated multiple programmes to develop vaccines against SARS-CoV-2 and its variants with a focus on speed, scale and access. These programmes leverage the rapid response platforms developed by CEPI’s partners prior to the emergence of COVID-19 as well as new collaborations. The aim is to advance clinical development of a diverse portfolio of safe and effective COVID-19 candidates and to enable fair allocation to these vaccines worldwide through COVAX. CEPI’s 5-year plan lays out a $3.5 billion roadmap to compress vaccine development timelines to 100 days, develop a universal vaccine against COVID-19 and other Betacoronaviruses, and create a “library” of vaccine candidates for use against known and unknown pathogens. About the CORAL Program Gritstone’s CORAL program is a second-generation SARS-CoV-2 vaccine platform delivering spike and additional SARS-CoV-2 T cell epitopes, offering the potential for more durable protection and broader immunity against SARS-CoV-2 variants. Delivery vectors can comprise a chimpanzee adenovirus, self-amplifying mRNA or both (mix and match). The program is supported by several key relationships: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Disease (NIAID), and the Coalition for Epidemic Preparedness Innovations (CEPI). An ongoing Gritstone-sponsored Phase 1 trial is evaluating SAM as a boost and immunogenicity enhancer of AstraZeneca's first-generation COVID-19 vaccine AZD1222 (Vaxzevria) in healthy adults ≥ 60 years in the UK. A two-dose SAM regimen is also being evaluated in an ongoing clinical trial sponsored by the National Institute of Health (NIH) Division of Microbiology and Infectious Disease and in the Coalition for Epidemic Preparedness Innovations-funded, Gritstone-sponsored clinical trial in South Africa expected to begin by year end 2021. About Gritstone Gritstone bio, Inc. a clinical-stage biotechnology company, is developing the next generation of immunotherapies against multiple cancer types and infectious diseases. Gritstone develops its products by leveraging two key pillars—first, a proprietary machine learning-based platform, Gritstone EDGETM, which is designed to predict antigens that are presented on the surface of cells, such as tumor or virally-infected cells, that can be seen by the immune system; and, second, the ability to develop and manufacture potent immunotherapies utilizing these antigens to potentially drive the patient’s immune system to specifically attack and destroy disease-causing cells. The company’s lead oncology programs include an individualized neoantigen-based immunotherapy, GRANITE, and an “off-the-shelf” shared neoantigen-based immunotherapy, SLATE, which are being evaluated in clinical studies. Within its infectious disease pipeline, Gritstone is advancing CORAL, a COVID-19 program to develop a second-generation vaccine, with support from departments within the National Institutes of Health (NIH), the Bill & Melinda Gates Foundation, the Coalition for Epidemic Preparedness Innovations (CEPI) and through a license agreement with La Jolla Institute for Immunology (LJI). Additionally, the company has a global collaboration for the development of a therapeutic HIV vaccine with Gilead Sciences. About COVAX COVAX, the vaccines pillar of the Access to COVID-19 Tools Accelerator, is co-convened by CEPI, Gavi, the Vaccine Alliance Gavi) and the World Health Organization – working in partnership with UNICEF as key implementing partner, developed and developing country vaccine manufacturers, the World Bank, and others. It is the only global initiative that is working with governments and manufacturers to ensure COVID-19 vaccines are available worldwide to both higher-income and lower-income countries.

Read More

Precision Virologics and Bharat Biotech Jointly Obtain Rights to Intranasal COVID-19 Vaccine Technology

Precision Virologics | September 23, 2020

Biotech startup Precision Virologics, which develops adenovirus-based vaccines in St. Louis, and Bharat Biotech, a vaccine manufacturing giant, jointly obtained rights from Washington University School of Medicine in St. Louis for a novel chimp-adenovirus vaccine for COVID-19. Precision Virologics has optioned rights for USA, Europe, and Japan. Bharat has obtained a license for all other markets. The licensing agreements will lead to rapid clinical development, following the intranasal vaccine candidate having shown unprecedented levels of protection in mouse studies. This technology and data recently was published in Cell and Nature. "The ability to accomplish effective immunization with a single nasal dose is a major advantage, offering broader reach and easier administration," said Precision Virologics Interim CEO David T. Curiel, MD, PhD. "An effective nasal dose not only protects against COVID-19, but it also prevents the spread of the disease by directly targeting the cells that line the nose and throat. Most other vaccine candidates currently under development can't do that." Based on these exceptional findings, the National Institutes of Health is advancing studies in non-human primates. Phase I trials – a single nasal dose – will take place at Saint Louis University's Vaccine and Treatment Evaluation Unit. Bharat Biotech, upon obtaining regulatory approvals, will pursue clinical trials in India and undertake large-scale manufacture of the vaccine at its GMP facility in Genome Valley, India.

Read More