Latus Bio Unveils AAV-Ep+ Capsid Variant Capable of Unprecedented Protein Production in the Brain
PHILADELPHIA--(BUSINESS WIRE)-- Latus Bio, Inc. (Latus), a biotechnology company pioneering advances in AAV gene therapy, has announced new research published today in Science Translational Medicine, 'AAVs engineered for robust brain transduction drive therapeutically relevant expression of secreted recombinant protein in NHPs and a mouse model of lysosomal storage disease.'
"This breakthrough in AAV capsid engineering represents a critical advancement in the field of gene therapy," said Dr. Beverly Davidson, Chair of the Scientific Advisory Board of Latus Bio and corresponding author of the study.
The study, led by Latus founder Beverly Davidson, PhD details the development of a novel adeno-associated virus (AAV) capsid variant - AAV-Ep+ - that demonstrates unprecedented potency in transducing cells that line the ventricles, known as ependymal cells, and cerebral neurons in mice and in non-human primates (NHPs). This advancement is potentially a significant leap forward for therapeutic gene delivery, wherein the study authors demonstrate that cells transduced with AAV-Ep+ can effectively serve as protein production depots, secreting large amounts of soluble proteins into the cerebral spinal fluid (CSF) for uptake throughout the central nervous system (CNS). This potency and distribution profile could potentially result in one-time delivery of gene therapies that encode protein treatments for lysosomal storage disorders (LSDs) as well as for other neurodevelopmental and neurodegenerative diseases that result in long term benefits for patients.
The AAV-Ep+ capsid variant was identified through a massively parallelled and unbiased screen of a large-diversity AAV variant library administered to NHPs. The nominated capsid, which was isolated from tens of millions of potential candidates, displays:
Remarkable tropism for cells that line the ventricular system of the brain and spinal cord of adult NHPs and mice. It also efficiently transduces neurons in cortical regions of the brain that are implicated in many diseases.
Robust transduction of induced pluripotent stem cell (iPSC)-derived human neurons and mice when compared to naturally occurring AAV serotypes. This cross-species activity highlights the potential for AAV-Ep+ to deliver sustained and therapeutic expression of encoded proteins in human brain cells that could result in prolonged therapeutic benefit for patients.
Low dose administration of AAV-Ep+ constructs designed to express human tripeptidyl peptidase (hTPP1) to mice deficient in TPP1 (a model of human CLN2 disease - a type of LSD) as well as to NHPs result in CSF and parenchymal tissue levels that exceeded those obtained with natural serotype capsids, reaching levels that are potentially multi-fold above therapeutic values required for CLN2 patients.
"This breakthrough in AAV capsid engineering represents a critical advancement in the field of gene therapy," said Dr. Beverly Davidson, Chair of the Scientific Advisory Board of Latus Bio and corresponding author of the study. "AAV-Ep+ offers a highly efficient, low-dose solution for brain-wide protein delivery, opening new possibilities for treating neurodevelopmental diseases like CLN2 disease and beyond."
The study showcases Latus' unique capsid discovery platform and ability to identify AAV capsid variants that are optimized for delivery to specific tissues and cell types, seeking to address translational shortcomings to prospectively enable better gene therapies. Latus continues to advance its pipeline of novel AAV capsid variants that target disease-relevant cell types in other regions of the central nervous system (e.g., cortex, cerebellum, spinal cord) as well as in peripheral tissues (e.g., ear, eye, heart, kidney and muscle). The Company is developing cutting-edge gene therapies that aim to transform the treatment landscape of genetically defined diseases, including many with high unmet medical needs.
About Latus Bio (Latus)
Latus is a biotechnology company dedicated to addressing devastating CNS and peripheral diseases via gene therapy. The Company is advancing an innovative therapeutics pipeline based on novel AAV capsid variants with potency and specificity. Latus is powered by a diverse team of visionary scientists, experienced clinicians, and leading industry executives. The Company has offices in Philadelphia, PA and in the Seaport in Boston, MA.
For more information, visit www.latusbio.com and follow on LinkedIn.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Yahoo
2 days ago
- Yahoo
Commit Biologics appoints leading industry experts to newly formed Scientific Advisory Board
Industry and scientific experts in molecular biology, immunology and antibody research appointed to help develop Commit's BiCE™ technology platform to treat autoimmune disease and cancer Leading antibody expert Janine Schuurman to co-chair Commit's Scientific Advisory Board alongside Commit's CEO Mikkel Wandahl Pedersen Joined by Paul Parren, Gavin Thurston, Susan Kalled, and Esper Boel on the Scientific Advisory Board AARHUS, Denmark, June 4, 2025 /PRNewswire/ -- Commit Biologics ("Commit"), a pioneer in the activation of the complement system to treat autoimmune disease and cancer, today announces the formation of its Scientific Advisory Board (SAB) with the appointment of five leading industry and scientific experts. The newly formed board will be co-chaired by leading antibody expert Janine Schuurman, PhD, and Commit's CEO Mikkel Wandahl Pedersen. They are being joined by Professor of Molecular Immunology, former Genmab SVP and serial biotech entrepreneur Paul Parren, PhD; former Regeneron SVP of Oncology Research Gavin Thurston, PhD; esteemed immunologist Susan Kalled, PhD, who has previously worked as CSO at both Dianthus Therapeutics and Compass Therapeutics; and molecular biologist Esper Boel, PhD, previously CTO at Symphogen and Corporate Vice President and Head of Biotechnology at Novo Nordisk. The SAB will provide constructive feedback to Commit's management team and Board of Directors as the Company further develops its Bispecific Complement Engager (BiCE™) technology platform. Mikkel Wandal Pedersen, PhD, Chief Executive Officer of Commit Biologics, said: "Forming Commit's Scientific Advisory Board is a pivotal step in our mission to bring first-in-class complement engager therapeutics to patients. I am very pleased that we have been able to gather such an accomplished group of people with deep immunology and drug-development experience. I am confident that their collective insight will sharpen our strategy and accelerate advancement of our pipeline." Scientific Advisory Board Janine Schuurman, PhD, is a molecular immunologist who has contributed to six FDA- and EMA-approved therapeutic antibodies, including four therapeutics from Genmab's DuoBody bispecific antibody platform. She spent 22 years at Genmab, most recently as Senior Vice President, Head of Antibody Research and Technology, propelling the discovery and development of investigational therapies to treat cancer and other diseases. Besides serving as an independent biotech consultant providing expert advice to a number of life sciences companies, Janine also serves as board member and President of The Antibody Society. Gavin Thurston, PhD, is a highly experienced R&D executive and scientific leader with over 20 years of experience in oncology research. He previously served as Senior Vice President of Oncology Research at Regeneron, where he played a pivotal role in the successful clinical development of LIBTAYO® and the ongoing late-stage clinical testing of seven other antibodies and bispecific antibodies. Following his time at Regeneron, Dr Thurston has been involved in a number of consultancy projects with antibody therapeutic companies. Paul Parren, PhD, is a molecular immunologist who has contributed to nine FDA- and EMA-approved therapeutic antibodies, including four therapeutics from Genmab's DuoBody bispecific antibody platform. He has spent over 25 years translating antibody knowledge into innovative therapies including 15 years at Genmab, where he headed preclinical R&D. More recently he was head of R&D at LAVA Therapeutics NV, which obtained a NASDAQ listing during his five-year tenure. He currently serves as Professor of Molecular Immunology at Leiden University Medical Centre in The Netherlands, is chairman of the board of The Antibody Society, provides expert advice and is a co-founder and CSO of Gyes BV and its two spin-out companies. Susan Kalled, PhD, is an immunologist with over 25 years of experience spanning early discovery research, clinical drug development and strategic partnerships in the areas of autoimmunity & inflammation, rare diseases and immuno-oncology. Previously she was CSO at Dianthus Therapeutics and Compass Therapeutics. As Vice President of Biology at Q32 Bio, Kalled established the founding research team and played a key role in shaping the company's complement and immunology-focused pipeline. She has also held a number of leadership positions at Biogen and Shire, driving scientific strategy. She currently serves as a scientific strategist and advisor to both early start-ups and established companies. Esper Boel, PhD, is a molecular biologist with 40 years of experience in international biopharmaceutical R&D. He spent 34 years at Novo Nordisk, most recently as Corporate Vice President and Head of Biotechnology. During this time, he was responsible for building and heading a 240+ employee international protein-biotechnology organisation and he established the first international biopharmaceutical R&D centre in Beijing, China. Following his time at Novo Nordisk, he has served as a member of executive teams, on boards and as a senior advisor for a number of high-profile immunology-based companies. Commit Biologics is advancing development of its BiCE™ technology to redefine the treatment of autoimmune disease and cancer. This novel platform is designed to potently activate the complement system to induce highly selective killing of cells implicated in autoimmune disease or tumour cells. BiCE™ uses single domain antibodies that bind to the complement protein C1q, consequently directing the complement system in a highly targeted way against cells of interest. The complement system is part of the body's immune system that has previously been largely untapped therapeutically. The activation of the classical complement pathway, which has a role in health for pathogen defence, begins with the engagement of C1q to antibodies that coat the cell surface, thus initiating multiple effector functions that lead to cell killing. About Commit BiologicsCommit Biologics (Commit) is a pioneer in activating the complement system to kill specific target cells, with applications in autoimmune diseases and cancer. Spun out of Aarhus University, and building on more than three decades of research, Commit's Bispecific Complement Engaging (BiCE™) platform can supercharge a conventional monoclonal antibody to activate the complement system more effectively. This is achieved by combining single domain antibodies that engage C1q, the starting point for the complement activation cascade, with an antibody that binds to a cellular target. The modular approach of the BiCE™ technology can be used to develop therapeutics across multiple tumour-associated antigens and immune cell targets. Complement is a largely untapped aspect of the body's natural immune system that leverages both the direct cytolytic activity of complement along with its ability to recruit and activate both innate and adaptive immune cells – a new approach to killing cells which can be used in combination or on a standalone basis. Commit is backed by major investors including Novo Holdings, Bioqube Ventures and Korys. About the complement systemThe complement system is part of the body's immune system that has previously been largely untapped therapeutically. The activation of the classical complement pathway, which has a role in health for pathogen defence, begins with the engagement of C1q to antibodies that coat the cell surface and ends with the activation of a cytolytic complement complex directly leading to cell lysis. However, current monoclonal antibodies developed for therapeutic purposes have structural restraints that hinder effective engagement to C1q, thus limiting complement mediated cytotoxicity and other complement mediated effector functions. This, plus the presence of natural cell bound complement inhibitors that are often upregulated in disease settings, and low target densities, make conventional therapeutic antibodies poor complement activators. Commit's BiCE™ technology was developed to overcome these barriers, to harness the power of the complement system and direct it towards tumour and immune cells for therapeutic applications. Unleashing this power in a highly targeted way with Commit's technology potentially allows for a broad therapeutic index and the development of highly effective treatments. View original content: SOURCE Commit Biologics Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Business Wire
3 days ago
- Business Wire
Affinia Therapeutics and DCM Foundation Announce Partnership to Increase Awareness About BAG3 Dilated Cardiomyopathy and Critical Need for Genetic Testing to Help Save Lives
WALTHAM, Mass. & DUBLIN, Ohio--(BUSINESS WIRE)--Affinia Therapeutics ('Affinia'), an innovative gene therapy company with a pipeline of first-in-class and/or best-in-class adeno-associated virus (AAV) gene therapies for devastating cardiovascular and neurological diseases, and the DCM Foundation together with the Genetic Cardiomyopathy Awareness Consortium (GCAC), today announced they have joined forces to raise awareness about BAG3 dilated cardiomyopathy (DCM), with the goal of promoting early diagnosis and the critical need for genetic testing. BAG3 DCM is a devastating monogenic heart disease affecting more than 70,000 patients in the U.S., Europe, and U.K. regions alone. The BAG3 gene, or Bcl2-associated athanogene 3, encodes for a protein that is critical to the normal structure and function of heart cells. Patients with BAG3 DCM have a mutation in the BAG3 gene and a deficiency in functional BAG3 protein, resulting in early onset heart failure that progresses rapidly. Despite current standard of care, almost 25% of patients require a heart transplant. According to a study published in Circulation, the journal of the American Heart Association, close to 50% of cardiomyopathy has some type of genetic basis, such as BAG3 DCM, yet only a fraction of diagnosed cardiomyopathy patients get genetic testing. This new-found partnership between Affinia and the DCM Foundation and GCAC aims to educate about BAG3 DCM and the critical need for genetic testing, and champions the needs and voices of people living with this devastating heart disease through initiatives including: BAG3 Patient Advisory Council to offer insight and feedback into patient needs and include the patient voice from people living with BAG3 DCM to inform research and clinical trial design. BAG3 DCM Webinar to help educate about genetics and cardiovascular disease, and the latest advances in research and development, with a focus on Affinia's pipeline and lead program for BAG3 DCM, AFTX-201. AFTX-201 is a potential best-in-class investigational AAV gene therapy intended to be given as a simple one-time intravenous injection. Genetic testing for BAG3 DCM to improve the diagnosis and management of patients affected with this devastating disease. 'The DCM Foundation and GCAC are very grateful for this partnership with Affinia,' said Greg Ruf, Founder and Executive Director, the DCM Foundation. 'By getting more cardiomyopathy patients tested, we can potentially save and improve lives and help advance cardiomyopathy research and therapies. Through this collaboration, we will collectively unite our strengths and work together in the hope of making a real difference for those living with this devastating disease.' Hideo Makimura, M.D., Ph.D., Chief Medical Officer of Affinia, commented, 'BAG3 DCM is a devastating heart disease with a known genetic cause. Unfortunately, only a fraction of patients affected with BAG3 DCM and other genetic cardiomyopathies are tested, which is putting lives at risk. We are committed to working together with the DCM Foundation and GCAC to increase disease awareness and the role genetics plays in cardiomyopathy, which we believe will ultimately lead to better outcomes for people living with BAG3 DCM.' 'Our partnership with the DCM Foundation and GCAC is an exciting milestone as we advance our lead program, AFTX-201 for BAG3 DCM, toward an Investigational New Drug submission and clinical trial initiation which are aligned with Affinia's purpose to make a lasting positive impact in the lives of people affected by devastating rare and prevalent diseases where the genetic cause is understood,' said Rick Modi, Affinia's Chief Executive Officer. About Affinia Therapeutics Affinia Therapeutics is pioneering a shift to a new class of rationally designed gene therapies that treat rare and prevalent diseases. Affinia Therapeutics' pipeline of first-in-class or best-in-class product candidates in cardiovascular and neurological diseases leverages its proprietary next-generation capsids, payloads, or manufacturing approaches and have shown efficacy, safety, and differentiation in relevant animal models. For more information, visit About DCM Foundation Founded in 2018, the DCM Foundation's mission is to provide hope and support to DCM patients and families with dilated cardiomyopathy through education, research and advocacy. Our mission is being executed through three foundational pillars: information and education, patient and family support, and understanding the need for genetic testing. In 2023, DCMF created the Genetic Cardiomyopathy Awareness Consortium, comprised of 11 patient group members, to address the extreme lack of knowledge about genetics and genetic testing in the cardiomyopathy patient and medical community. For more information, visit and
Scientific American
4 days ago
- Scientific American
Engineered Viruses Make Neurons Glow and Treat Brain Disease
The brain is like an ecosystem—thousands of different types of cells connect to form one big, interdependent web. And just as biologists document species of plants and animals, neuroscientists have spent decades identifying different 'species' of neurons and other brain cells that support them. They've found more than 3,000 cell types spread throughout the brain, including chandelier neurons surrounded by branching arms, pyramidal neurons with far-reaching nerve fibers and star-shaped astrocytes that help neurons form new connections with one another. This newfound diversity is not only a beautiful picture for neuroscientists—it's also key to understanding how the brain works and what goes wrong in certain brain diseases. From Parkinson's disease to schizophrenia, many brain disorders stem from specific types of brain cells. 'As long as I've been doing neuroscience, it's been a goal of researchers to have brain-cell-type-targeting tools,' says Jonathan Ting of the Allen Institute, a nonprofit research center in Seattle. Now they have them in spades. In a fleet of eight studies funded by the National Institutes of Health and published last week, scientists from 29 research institutions found and tested more than 1,000 new ways to home in on specific cell types, no matter where they are in the brain. On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. The technique behind these tools uses non-disease-causing viruses (called adeno-associated viruses, or AAVs) to deliver genes directly to specific neurons. This can make the cells do almost anything. Scientists can turn them off, activate them, 'light them up like a Christmas tree' with glowing proteins or deliver gene therapies right to them, says Ting, senior author of one of the new studies. The researchers have tested the technique only in nonhuman animals, but the bulk of the tools work across mammal species and would likely work in humans, too. Similar, less-targeted AAV gene therapies are already approved for treating spinal muscular atrophy and are being tested in clinical trials for Huntington's disease. 'There are a lot of good examples' of how AAVs are being used to treat brain disease, says Nikolaus McFarland, a neurologist at the University of Florida, who treats neurodegenerative diseases such as Parkinson's and Huntington's. 'It's really exciting stuff.' Viral Shuttles Every type of brain cell is like a unique creature. Scientists have categorized the cells based on their shape, location and electrical properties—and, more generally, based on the genes they express most out of an organism's full library of DNA. By expressing certain genes, these cells carry out specific actions, such as building specialized proteins. If researchers can identify a unique snippet of genetic code that is activated just in those cells, they can use that snippet to target them. Next, they attach this genetic snippet, called an enhancer, to an AAV that has been gutted of its viral DNA. They can fill the viral husk with specific genes to deliver to those cells. The now-filled husks enter the bloodstream like a fleet of delivery shuttles, bypassing the blood-brain barrier, but are only able to activate their genetic cargo in cells with the enhancer. In the new studies, researchers focused on cell types in three parts of the brain: the outer layer of brain tissue called the cortex that plays a role in higher-level thinking, the striatum, which is part of the basal ganglia (a stretch of deep brain tissue) that is impacted in Huntington's and Parkinson's disease, and the spinal cord, whose motor neurons are destroyed in amyotrophic lateral sclerosis (ALS). The consortium of 247 scientists was funded by the NIH's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative as a part of a larger research project called the Armamentarium for Precision Brain Cell Access. The scientists found and tested more than 1,000 enhancer AAVs, now freely available to researchers, that target specific cell types in those key brain regions. Tweaking the Brain Previously, these enhancer AAVs had been developed in a slow trickle by different labs, but 'now we have thousands of tools' to tweak specific cell types, says Bosiljka Tasic, director of molecular genetics at the Allen Institute and senior author of one of the new studies. Researchers can load these AAV shuttles with all sorts of different genes to answer different questions. In some cases, even just seeing the neurons in action is cause for celebration: 'Some of them are very rare cells that you wouldn't find randomly by poking around in brain tissue,' Ting says. To observe them, researchers can introduce a gene that makes a glowing protein that lights up elusive neurons from the inside to reveal their structure and how they connect with other brain cells. Researchers can also control how certain brain cells fire and turn their activity up or down to see how the change impacts an animal's behavior. To do this, researchers insert a gene into the target cells that creates a light-sensitive protein called an opsin; then they can shine specific wavelengths of light on the brain to make those cells fire on command. Ting's team used this technique, called optogenetics, to stimulate certain cells in the striatum of mice. When the researchers stimulated those cells on just one side of the brain, the mice began moving more on one side of their body than the other, causing them to go in circles. These interventions are reversible and repeatable. 'That's the part that's really satisfying for neuroscientists,' Ting says. 'You can turn them off, turn them back on and then see how that affects the brain circuit.' It's ' so much better and also so much more informative' than destroying whole parts of a mouse brain to see what happens, as is the case with much neuroscience research from the past century, Tasic says. 'That brain region may have a hundred different cell types,' so being able to activate and inactivate them more precisely will reveal more information about how these circuits work, she says. New Treatments So far, the new enhancer AAVs have been tested in mice, rats and macaques. 'We keep trying more and more species,' Ting says. 'We haven't even figured out what's the limit.' And that brings us to humans. 'That's really the answer to the question 'Why do we care?'' he says. 'We have built strong evidence that some of these tools—maybe not all of them, but many of them—may work across species into humans and could represent the start of a new therapeutic vector development that could be used to more finely treat debilitating brain disorders.' For these treatments, enhancer AAVs could deliver gene therapy right to the brain cells that need it. The best candidates for this technique are neurodegenerative diseases, such as ALS, Parkinson's disease and Huntington's disease. Researchers are currently working on AAV gene therapies for these conditions and others that target whole regions of the brain rather than specific types of brain cells. Trials of these therapies indicate that they are largely safe. 'We now have lots of good examples of AAV being used,' McFarland says. 'We have [a] good safety record for that.' 'There's a lot that we still don't understand about neurodegenerative diseases,' he adds, and these little viral shuttles will allow scientists to make those discoveries that enable new treatments. While each of these brain disorders is unique, cracking one of them might help scientists crack the others, too, McFarland says: 'I wholeheartedly believe that.'
