Realization of new image-based structure analysis method for 3-D structural analysis of biology

Phys.org | October 03, 2019

In basic biology, medical sciences and pharmaceutical sciences, structural analyses of membrane proteins are important, and single-particle analysis by cryoEM is now very powerful method. Japanese researchers have developed the image-based structure analysis (IBSA) method, an improved method of single-particle analysis that enables structural analysis in a lipid membrane. This development has made it possible to analyze the structures of membrane proteins in vivo. Single-particle analysis, a cryo-electron microscopy method, does not require crystallization of the sample as in X-ray crystal structure analysis, and there is no upper limit on the molecular weight of the sample as in nuclear magnetic resonance spectroscopy. Since atomic resolution can be achieved with very few aqueous samples, single-particle analysis has established a position as one of the basic technologies for structural analysis. However, this method requires a large number of images of randomly placed target protein particles. Purification of proteins is necessary in single-particle analysis and in the case of membrane proteins, detergent solubilization is required for this purification. This changes the molecular structure. Therefore, it is difficult to analyze the structure of membrane proteins in a real environment.

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Sequencing of human genomes is fast becoming an affordable technology for general consumer.

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Sequencing of human genomes is fast becoming an affordable technology for general consumer.

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RESEARCH

Skye Bioscience Establishes New Cannabinoid Pharmaceutical Innovation Program

Skye Bioscience, Inc. | October 13, 2021

Skye Bioscience, Inc. (“Skye” or the “Company”), a biopharmaceutical company developing proprietary, synthetic cannabinoid-derived molecules to treat glaucoma and other diseases with significant unmet need, has formed a new exclusive sponsored research agreement with Emerald Health Biotechnology Espana SLU (“EHBE”), focused on developing and characterizing novel molecules that can affect the endocannabinoid system (ECS) for therapeutic benefit. The research initiative, referred to as the Cannabinoid Pharmaceutical Innovation Program (CPIP), will focus on targeting important signaling pathways in the endocannabinoid system to realize therapeutically beneficial effects. The CPIP reflects the company’s continued commitment to expand its leadership in cannabinoid-based science and cutting-edge research that can be commercialized through new and existing technologies. It leverages R&D initiatives with key opinion leaders with specialized research centers in the US and internationally, such as the University of Mississippi, University of Cordoba, and University of Eastern Piedmont. This agreement deepens the commitment of Drs. Munoz and Appendino, who will be the principal investigators and continue to lead Skye’s scientific advisory board. The CPIP is driven by the focus on investing in key value-creating pillars for the Company - ophthalmology applications, clinical development, pipeline expansion and people - to achieve the vision of creating a world-class cannabinoid pharmaceutical company. "As the world comes to appreciate the broad and dynamic role of the endocannabinoid system in humans and animal health, the pharmaceutical potential of cannabinoids to modulate this system is just starting to be understood. While the anecdotal evidence of the health benefits of cannabinoids dates back millenia, modern science has barely scratched the surface to validate the benefits of the ECS in preventing and treating diseases. Skye’s ambition is to play a leading role in effecting important therapeutic outcomes by influencing the endocannabinoid system. We want to continue to make strategic investments that can further bring value to all stakeholders, and our clear focus in this initiative is to achieve novel discoveries that achieve important clinical utility with commercial value. These overarching priorities will guide our strategy, project initiatives, and investments." Punit Dhillon, Chief Executive Officer and Chair of Skye Bioscience Under the terms of the agreement: Skye will approve and fund designated projects and have exclusive rights to all data and products, and any intellectual property resulting from this research collaboration will be owned by Skye Research will be broad and encompass novel molecules that modulate the ECS to treat or prevent human or animal diseases EHBE will receive a single digit royalty on all licensing revenue or other consideration paid to Skye by a third-party licensee, assignee or purchaser related to any product commercialized as part of a Skye Project Skye will pay EHBE a retainer of $200,000 per year. “Having worked with cannabinoids and the endocannabinoid system for over 25 years, it is clear that there are tremendous opportunities to discover and create cannabinoid-derived molecules with potential to beneficially interact with the ECS for positive medical outcomes. With the launch of Skye’s new Cannabinoid Pharmaceutical Innovation Program with our research team in Cordoba, Spain, our efforts will focus on preclinical development of CBDVHS, R&D of CB1 modulators involved in pain, inflammatory diseases, neurological diseases, fibrotic diseases and metabolic diseases, and drug discovery relating to modulators of the cannabinoid receptors CB2 and GPR55. We aim to generate a wide portfolio of proprietary products and IP around molecules with commercial potential.” Eduardo Munoz, Managing Director of Emerald Health Biotechnology Espana About Emerald Health Biotechnology Espana SLU Emerald Health Biotechnology España SLU (EHBE) is a preclinical-stage drug development research company focused on new cannabinoid derivatives to treat severe life-threatening conditions and other pathologies. Led by cannabinoid research experts and scientific advisors to Skye, Drs. Eduardo Munoz and Giovanni Appendino, EHBE is a pioneer in developing chemical cannabinoid derivatives that improve the therapeutic properties of the natural compounds. About Skye Bioscience Skye Bioscience Inc. is a biopharmaceutical company unlocking the pharmaceutical potential of cannabinoids through the development of its proprietary, cannabinoid-derived molecules to treat diseases with significant unmet needs. The company’s lead program, THCVHS, is focused on treating glaucoma, a disease with no cure and the world’s leading cause of irreversible blindness. For more information, please visit: www.skyebioscience.com

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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.

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INDUSTRIAL IMPACT

BioAuxilium Research Expands its No-Wash THUNDER™ TR-FRET Cell Signaling Assay Portfolio

BioAuxilium Research Inc. | February 10, 2022

At the annual Society for Laboratory Automation and Screening International Conference and Exhibition in Boston, BioAuxilium Research Inc., a biotech tool company focused on facilitating access to fully validated assay kits to the biomedical research community, today announced the expansion of its no-wash THUNDER™ time-resolved Förster resonance energy transfer technology portfolio by introducing new cell signaling pathway and biomarker research assay kits, along with a panel of “mix and match” toolbox reagents. The new offerings bring the company’s portfolio to a total of 104 products. Developed and manufactured at BioAuxilium’s laboratories, the new THUNDER™ TR-FRET assay kits are ideal for studying intra- or extra-cellular signaling pathways and include key human kinases, pro-inflammatory cytokines, and a cAMP detection kit designed for the screening and characterization of G‑protein coupled receptors (GPCRs). The THUNDER™ TR-FRET toolbox reagents include europium and far-red labeled anti-species, anti-epitope, and streptavidin for enabling easy in-house assay development. “The addition of the new THUNDER™ TR-FRET assays and reagents demonstrate our capacity to continue to grow a focused portfolio of high quality yet affordable assays for both basic research and drug discovery. In addition, we are committed to addressing the reproducibility crisis in biomedical research by continuing to provide reliable research tools that enable the generation of highly reproducible results, much faster.” Jaime Padros, PhD, President, BioAuxilium Research BioAuxilium’s THUNDER™ TR-FRET technology is a robust, proprietary platform based on a FRET pair showing an enhanced spectral compatibility and TR-FRET signal, optimal antibody pairs selected specifically for TR-FRET, and a panel of optimized lysis and assay buffers. In addition, all assays use a simplified protocol that dramatically decreases hands-on time and assay variability and is easily amenable to automation for high-throughput screening. All THUNDER™ TR-FRET products are extensively validated to ensure specificity, sensitivity, and reproducibility using real-life biological samples. About BioAuxilium Research Inc. BioAuxilium is a private Canadian biotechnology tool company founded by expert assay scientists. It focuses on developing and manufacturing top-quality, highly validated assay kits that accelerate biomedical research. BioAuxilium’s kits are based on its enhanced proprietary THUNDER™ TR-FRET technology. They are offered at an outstanding value and are accompanied by information-rich datasheets and expert technical support. Bioauxilium also provides customized services in assay development using diverse technologies on a contract basis.

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