
AexeRNA Therapeutics is developing novel mRNA therapeutics and vaccines, leveraging a proprietary high-potency targetable mRNA lipid nanoparticle delivery platform technology: the AexLNP System
The AexLNP System consists of a rapidly screenable rationally designed library of highly potent ionizable AexLipids having low reactogenicity and the AexBoost LNP potency multiplying manufacturing process. The AexLNP System is currently being further developed to provide ligand-mediated cell/tissue targeting.
Thus, the AexLNP System is a comprehensive best-in-class mRNA delivery tool kit that opens new therapeutic applications and provides the optimal LNP for any given therapeutic application.
AexeRNA Product Development: We developing our own infectious diseases vaccines and mRNA therapeutics in other areas such oncology and rare genetic disease.
Linden Lake Venture Capital aims to found, build and invest in the next-generation of biotechnology companies bringing transformative new molecular medicines to patients in need.
Thomas is a Co-Founder and the CEO of AexeRNA Therapeutics. He is also Managing Member of Linden Lake Venture Capital and a veteran biotechnology executive, investor, entrepreneur and intellectual property lawyer. Previously, he was a co-founder, and Interim CEO of PhosImmune, Inc., an immuno-oncology company acquired by Agenus, Inc. (NASDAQ: AGEN). Thomas also served as General Counsel of Arrowhead Research Corporation (now Arrowhead Pharmaceuticals NASDAQ: ARWR) and represented Arrowhead during its acquisition of Roche's RNAi business unit. Thomas practiced law at Fanelli Haag PLLC, McDermott Will & Emery LLP and Kenyon & Kenyon LLP. He earned a B.S. in Biology and Ph.D. in Molecular, Cell & Developmental Biology from UCLA where he was an NIH Fellow in Genetics. He also graduated from George Washington University Law School.
Mohamad-Gabriel is a Scientific Co-Founder and interim Chief Scientific Officer of AexeRNA Therapeutics. He received B.S. and M.S. degrees from the University of Montreal, and a Ph.D. in Biomedical Engineering from Polytechnique Montreal in Mike Buschmann's lab. His thesis work focused on understanding the intrinsic and extrinsic parameters affecting chitosan-siRNA nanoparticle macromolecular properties. Mohamad-Gabriel joined Drew Weissman's at the University of Pennsylvania as a Postdoctoral Fellow in 2018, where he leads multiple vaccine projects as Assistant Research Professor. He is also Co-Director, of the Engineered mRNA and Targeted Nanomedicine Core at the University of Pennsylvania
Mike is a Scientific Co-Founder and was the Chief Scientific Officer of AexeRNA Therapeutics. He was also the Department Chair, and Eminent Scholar of the Volgenau School of Engineering at George Mason University. He had over 20 years of experience in developing biomaterials for tissue repair and nucleic acid delivery at École Polytechnique in Montreal. Mike earned his Ph.D. in Medical Engineering and Medical Physics from the Massachusetts Institute of Technology in the Harvard-MIT Division of Health Sciences and Technology and conducted his postdoctoral studies at the ME Mueller Institute of Biomechanics, University of Bern, Switzerland. He was co-inventor of the cartilage repair product CarGel, sold by Smith & Nephew and co-founder of Ortho Regenerative Technologies Inc. which develops other tissue repair products.
Drew is a Scientific Co-Founder and Scientific Advisor to AexeRNA Therapeutics. He is a physician-scientist and pioneer in the science of immunology, with major contributions to the field. Notably, Drew and his colleagues discovered a novel nucleoside-modified mRNA platform that bypasses adverse immunologic response. The result of decades-long dedication and research, this platform now serves as the basis for the burgeoning research of targeted therapeutics for some of the world’s most devastating diseases. This research outcome paved the way for the first mRNA vaccines, being the critical backbone to the COVID-19 mRNA vaccines. Drew and his lab team continue to conduct basic science research to understand and develop new nucleoside-modified mRNA platforms to advance effective and safe vaccines for different types of diseases, as well as new therapeutics.
Drew is the recipient of multiple accolades in medicine and research, including the NIH Merit Award, NIH Special Achievement Award, and the 50th Rosenstiel Award for Distinguished Work in Medical Science. Drew earned a B.S. at Brandeis University and M.D. and Ph.D. degrees at Boston University. He completed completed a residency in internal medicine at Beth Israel Hospital in Boston and a fellowship in allergy/immunology at the National Institutes of Health (NIH) under Dr. Anthony Fauci
Mikell is a Scientific Co-Founder and Advisor to AexeRNA Therapeutics. He is also Professor of Chemistry & Biochemistry at George Mason University and Co-Director of its Center for Drug Discovery and Rare Diseases. He is an expert medicinal chemist with experience in the design and synthesis of small molecule modulators of dysfunctional enzymes. He completed a Ph.D. in Organic Chemistry at the University of Virginia and post-doctoral training at Georgetown University.
Suman is a Scientific Co-Founder of AexeRNA Therapeutics. He is also Assistant Research Professor of Chemistry and Biomedical Engineering at George Mason University. Suman. Alishetty completed his Postdoctoral Fellowship in the labs of Dr. Michael Buschmann and Dr. Mikell Paige at George Mason. There he developed expertise in fine tuning lipids for improved lipid nanoparticle performance. His work includes the design and synthesis of corresponding water-soluble analogues to determine pKa and other physicochemical properties of novel components in mRNA delivery systems. He also designs, synthesizes, formulates, and characterizes novel lipids for the development of next generation lipid nanoparticles. He received his B.S. degree from Osmania University, India and M.S. in Industrial Chemistry from Jawaharlal Nehru Technological University in Hyderabad, India. He completed his Ph.D. in Organic and Material chemistry at the National Tsing Hua University in Hsinchu, Taiwan.
• High potency mRNA delivery
• Control of systemic distribution to various organs
• Ligand-mediated cell/organ specific targeting
• Low toxicity opening new therapeutic widows
• Improved thermal stability
• Rationally-designed proprietary ionizable lipid library
• The ability to quickly select the optimal AexLipid for each therapeutic application
• Proprietary LNP assembly methods for multiplying LNP potency
• Does not change the chemical composition of an LNP
• Combinable with to currently available lipids such as KC2, MC3 as well as AexLipids
AexeRNA Therapeutics is shocked and saddened to report the unexpected death of our co-founder and Chief Scientific Officer Prof. Michael Daro Buschmann. Mike was giant in his field, a shooting star at GMU, and a visionary in RNA therapeutics. His scientific brilliance and entrepreneurial leadership provided AexeRNA’s beating heart. He was, however, first and foremost a kind and humorous person with unflinching integrity. AexeRNA will continue to ensure that Mike’s scientific legacy plays a major role in the next generation of RNA based therapeutics.
Abstract: Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure ofthe ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium.We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.
Abstract: The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is in part due to the development of lipid nanoparticle delivery systems that not only efficiently express the mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and in vaccine reactogenicity. We present an overview of mRNA delivery systems and then focus on the lipid nanoparticles used in the current SARS-CoV-2 vaccine clinical trials. The review concludes with an analysis of the determinants of the performance of lipid nanoparticles in mRNA vaccines. Buschmann et al., Vaccines 2021, 9(1), 65
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