Breakthrough shines light on disease-fighting protein

Phys.org | February 25, 2019

X-ray and electron microscopy techniques help unfold the story of protein chaperones. A combination of X-ray crystallography and cryo-electron microscopy (cryo-EM) assisted in a collaborative effort to obtain the highest-resolution structure of the fungal protein Hsp104, which may serve to hinder the formation of certain degenerative diseases. The team, whose members included researchers from the U.S. Department of Energy's (DOE) Argonne National Laboratory, also verified a helical structure for the protein-formed hexamers, once believed flat. The results were published online in the Dec. 27, 2018 issue of Structure.
Hsp104 is a hexameric AAA+ protein known as a chaperone, which helps in the natural folding processes of proteins for proper cell function. More importantly, perhaps, this class of hexamers can repair misfolded or aggregated proteins that can lead to protein-caused abnormalities like neurodegeneration.

Spotlight

Scientists are genetically engineering plants to detect environmental hazards. Neal Stewart, a lead researcher on the project, says the plants will react to things like mold, radon gas, or high levels of dangerous organic compounds. Stewart told Science Update the goal is to create an on-off switch in the plants’ DNA. This means its cells would react to exposure of a chemical by producing a signal like a fluorescent protein visible by black light. There are a number of benefits to using a plant instead of an electronic device to monitor your personal space. Popular Mechanics pointed out that plants, unlike home assistants like Amazon’s Alexa, “are not connected to the cloud and definitely can’t hear what you’re saying.”

Spotlight

Scientists are genetically engineering plants to detect environmental hazards. Neal Stewart, a lead researcher on the project, says the plants will react to things like mold, radon gas, or high levels of dangerous organic compounds. Stewart told Science Update the goal is to create an on-off switch in the plants’ DNA. This means its cells would react to exposure of a chemical by producing a signal like a fluorescent protein visible by black light. There are a number of benefits to using a plant instead of an electronic device to monitor your personal space. Popular Mechanics pointed out that plants, unlike home assistants like Amazon’s Alexa, “are not connected to the cloud and definitely can’t hear what you’re saying.”

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MEDICAL

Thermo Fisher Scientific and Qatar Genome Program Partner to Advance Precision Medicine

Thermo Fisher Scientific | May 24, 2022

Thermo Fisher Scientific, the world leader in serving science, and Qatar Genome Program (QGP), a member of Qatar Foundation (QF), have partnered with the goal of accelerating genomic research and clinical applications of predictive genomics in Qatar as a step toward expanding the benefits of precision medicine across Arab populations globally. Under the agreement, Thermo Fisher and Qatar Genome Program will develop an Axiom* custom genotyping array for pan-Arab populations using whole genome sequencing data from 19 Arab countries. The array, with about 800,000 variants, aims to help drive scientific research and insights into conditions including diabetes, cardiovascular and metabolic diseases, autism, inherited genetic disorders and cancer. Once available through Thermo Fisher’s global commercial channels in late 2022, the array is intended to provide a cost-effective alternative to whole genome sequencing for Arab populations, enabling increased diversity in large genome-wide studies. Qatar’s national vision is to provide a high standard of living for our people, and that includes providing access to genomics data, technology and insights to improve population health across the country, Our collaboration with Thermo Fisher will not only help us advance precision medicine in Qatar but also among people of Arab identity worldwide.” Dr. Radja Badji, genome operations manager at Qatar Genome Program. Thermo Fisher began working with Qatar Genome Program in 2018 to establish the first microarray designed specifically for the Qatari population. The Q-Chip detects genetic alterations that increase individuals’ risk of both prevalent and rare diseases. As part of the new agreement, the organizations will continue to refine algorithms and define clinically actionable content to assess polygenic risk scores, a measure of disease risk, and clinically relevant variants, including those related to pharmacogenomics. Thermo Fisher’s Axiom microarray technology is designed to help accelerate precision medicine, and we are honored to partner with the Qatar Genome Program as they take bold steps to leverage the power of genomics to improve the standard of care for human health, Together, we’re creating building blocks for implementing comprehensive precision medicine initiatives at scale for population health.” Chad Carter, vice president and general manager of microarray genetic solutions at Thermo Fisher Scientific. About Thermo Fisher Scientific Thermo Fisher Scientific Inc. is the world leader in serving science, with annual revenue of approximately $40 billion. Our Mission is to enable our customers to make the world healthier, cleaner and safer. Whether our customers are accelerating life sciences research, solving complex analytical challenges, increasing productivity in their laboratories, improving patient health through diagnostics or the development and manufacture of life-changing therapies, we are here to support them. Our global team delivers an unrivaled combination of innovative technologies, purchasing convenience and pharmaceutical services through our industry-leading brands, including Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific, Unity Lab Services, Patheon and PPD. About the Qatar Genome Program The Qatar Genome Program is an ambitious population-based project aimed at positioning Qatar among the pioneering countries in the implementation of precision medicine. Whole genome sequencing and other omics data is being combined with phenotypic data within the Qatar Biobank, providing a resource for breakthrough research discoveries and to help policy makers set future healthcare priorities for Qatar.

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CELL AND GENE THERAPY

Merck and Orna Therapeutics Collaborate to Advance Orna’s Next Generation of RNA Technology

Merck and Orna Therapeutics | August 17, 2022

Merck known as MSD outside the United States and Canada, and Orna Therapeutics, a biotechnology company pioneering a new investigational class of engineered circular RNA therapies, today announced a collaboration agreement to discover, develop, and commercialize multiple programs, including vaccines and therapeutics in the areas of infectious disease and oncology. Under the terms of the agreement, Merck will make an upfront payment to Orna of $150 million, which will be expensed by Merck in the third quarter of 2022 and included in non-GAAP results. In addition, Orna will be eligible to receive up to $3.5 billion in development, regulatory, and sales milestones associated with the progress of the multiple vaccine and therapeutic programs, as well as royalties on any approved products derived from the collaboration. Orna will retain rights to its oRNA-LNP technology platform and will continue to advance other wholly owned programs in areas such as oncology and genetic disease. Merck will also invest $100 million of equity in Orna’s recently completed Series B financing round. Orna’s proprietary oRNA technology creates circular RNAs from linear RNAs by self-circularization. oRNA molecules have been shown to have greater stability in vivo than linear mRNA and have the potential to produce larger quantities of therapeutic proteins inside the body. Newly synthesized oRNA molecules are more compactly packaged into custom lipid nanoparticles which Orna has engineered to target key tissues in the body. Preclinical data, including presentations at the 2022 American Society of Gene & Cell Therapy Annual Meeting, have demonstrated the potential of oRNA expression and delivery as an approach for further development in multiple areas, including vaccines and oncology therapeutics. “This broad strategic collaboration brings together Merck’s significant expertise in nucleic acid biology, clinical development, and manufacturing with Orna’s compelling circular RNA technology to explore the opportunity to develop a new generation of potential vaccines and therapeutics. We look forward to working with the talented scientific and technical teams at Orna." Fiona Marshall, senior vice president and head of discovery, preclinical and translational medicine at Merck Research Laboratories “We are thrilled to collaborate with Merck, a company committed to breakthrough science, which has recognized the potential our platform can bring to patients. Our oRNA technology plus novel delivery solutions are designed to unlock the full potential of RNA in therapeutics and vaccines,” said Tom Barnes, Chief Executive Officer of Orna. “The combined expertise of Orna and Merck aims to accelerate the development of RNA therapeutics for patients in need of better treatment options.” About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. About Orna Therapeutics Orna Therapeutics was founded on groundbreaking research by Alex Wesselhoeft, Ph.D., and Daniel G. Anderson, Ph.D. from MIT and built by MPM Capital and BioImpact Capital, an investment management affiliate of MPM. Orna’s proprietary circular RNA (oRNA) is engineered as linear RNA that self-circularizes. By taking a line and turning it into a circle, oRNA exhibits numerous advantages over traditional linear mRNA therapies such as simplified production, increased protein expression, and a superior immunogenicity profile. With proprietary lipid nanoparticles including those from Orna’s joint venture with ReNAgade Therapeutics, an RNA delivery company, our technologies expand the possibilities of what RNA therapeutics can achieve.

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MEDTECH

Synthego Launches Engineered Cell Libraries to Validate Targets with Speed and Accelerate Drug Discovery

SYNTHEGO | August 03, 2022

Synthego, the genome engineering company, announced the launch of Engineered Cell Libraries, a novel offering that further enables access to CRISPR by providing arrayed CRISPR-edited cells for direct use in functional screening assays. The innovative solution leverages Synthego’s Eclipse™ Platform. This high-throughput cell engineering platform delivers cell-based models for disease research by providing highly predictable CRISPR-engineered cells at scale through the integration of engineering, bioinformatics, and proprietary science. Synthego’s Engineered Cell Libraries provide unparalleled speed, scalability, and efficiency to accelerate the drug discovery process by enabling a faster path between experimental design and execution. As the newest addition to Synthego's Engineered Cells product line, the offering is a custom arrayed library of multi-guide™ knockout cell pools (immortalized or iPSC) delivered ready-made to researchers, efficiently enabling them to bypass the need for equipment and reagent sourcing, transfection, generation of an extensive CRISPR library, and hiring and training of staff. This allows researchers to overcome common hurdles associated with CRISPR-based target discovery and focus specifically on the science. “Arrayed screening approaches are more sensitive, compatible with a broader assortment of downstream assays, and can yield data that is more readily interpretable than the more commonly used pooled approach but are underutilized due to lack of infrastructure and limited bandwidth. With Engineered Cell Libraries, Synthego continues to provide transformative solutions for accelerated drug discovery which ultimately can bring a wider range of therapeutics to market faster.” Travis Maures, Synthego’s Chief Technology Officer With Engineered Cell Libraries, scientists specify the human or mouse cell type (Immortalized or iPSC available at launch) and gene targets they desire to knockout to generate a custom “Knockout Cell Library.” The cells are then edited on Synthego’s Eclipse Platform, which handles guide design, cell line optimization, editing through transfection, and assessment of editing efficiencies, so cells are ready to screen upon arrival. Engineered Cell Libraries on the Eclipse Platform additionally benefit customers with Scalability and flexibility - Engineered Cell Libraries allow researchers to maximize their screening power and identify more targets earlier in the screening process. Predictability and transparency - Synthego’s multi-guide™ technology achieves reliably high knockout efficiencies so researchers can confidently proceed with their screens. Cell engineering expertise and support - Synthego uses its expertise to bring automation innovation that provides greater consistency in outcomes and scalability. Synthego’s Eclipse Platform and Engineered Cell Libraries enable a wide range of applications in research and development across various disease areas and research disciplines such as oncology and neurology. Engineered Cell Libraries were employed in a recent study that used genetic screening to identify host factors that either facilitate or inhibit infection by SARS-CoV-2 and that could potentially be targeted with existing drugs that have been approved for other indications. “We were able to quickly combine our proteomic expertise with Synthego's genome engineering capabilities in a matter of weeks,” said Nevan J. Krogan, Director, Quantitative Biosciences Institute, University of California, San Francisco. “Normally, work such as this would take many years. We were able to quickly pinpoint which human genes are important for infection, and that allowed us to jump to which ones if we were able to drug them, could have a positive pharmacological effect on SARS-CoV-2 infection. That whole pipeline allowed us to identify several potential drug candidates, several of which we're still looking at.” Ultimately, Synthego’s goal is to enable scientists to spend less time thinking about method development and more time running their functional assays. The addition of Engineered Cell Libraries is driving impact in biopharma research and development. ABOUT SYNTHEGO Synthego was founded to revolutionize genome engineering technology, helping translate genomics into the clinic and ultimately making engineered biological therapies accessible to all patients. The company leverages machine learning, automation, and gene editing to build platforms for science at scale. With its foundations in engineering disciplines, the company’s platforms vertically integrate proprietary hardware, software, bioinformatics, chemistries, and molecular biology to advance both basic research and therapeutic development programs. With its technologies cited in more than a thousand 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.

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