Boston– Permeasis Therapeutics and The Ohio State University have published foundational research on a technology designed to deliver therapeutic peptides and proteins directly into cells.
The peer-reviewed study, published in ACS Chemical Biology, describes Permeasis’ proprietary Membrane Translocation Domain platform and its potential to overcome a major obstacle in drug development: transporting biologic medicines across cellular membranes and into the cytosol and nucleus.
Most disease-driving proteins are located inside cells and remain inaccessible to conventional biologic therapies, including antibodies that primarily target proteins outside cells. This barrier has limited the development of protein therapeutics, enzyme replacement therapies, gene-editing systems and targeted protein degraders.
The publication, titled “Intracellular Delivery of Peptides and Proteins with an Engineered Membrane Translocation Domain,” is the first comprehensive report on the MTD platform. The technology was invented in the laboratory of Dehua Pei, PhD, distinguished professor of chemistry and biochemistry at Ohio State and co-founder of Permeasis Therapeutics.
“One of the fundamental challenges in biotechnology has been finding a safe and efficient way to deliver biologic medicines inside cells,” said Pei. “Our work demonstrates a potentially generalizable solution that can transport functional proteins across cellular membranes and into the intracellular compartment where most disease biology occurs.”
The study found that MTD can be genetically fused to a range of protein cargos while preserving their biological function. In preclinical studies, the platform delivered active enzymes, intracellular protein inhibitors and therapeutic proteins into cells and tissues.
The technology also demonstrated broad biodistribution following systemic administration in animal models and achieved intracellular delivery at low nanomolar concentrations, according to the company.
Permeasis was founded to translate the platform into intracellular biologic medicines capable of reaching previously inaccessible targets. Researchers from Ohio State and the company collaborated on the published studies.
“This publication describes foundational technology from Pei’s laboratory that Permeasis is continuing to mature as we work to develop a new class of therapeutics based on delivering intracellular proteins,” said Lou Tartaglia, PhD, a member of Permeasis Therapeutics’ Board of Directors. “Realizing the full therapeutic potential of biologics will require robust solutions for intracellular delivery, and we believe the MTD platform has the potential to help enable the next generation of protein-based medicines.”
“The ability to deliver proteins inside cells has been a longstanding goal across the biotechnology industry,” said Jeno Gyuris, PhD, chief scientific officer at Permeasis Therapeutics. “What is significant about MTD is its ability to move beyond traditional protein delivery approaches by enabling efficient escape from endosomal trafficking and delivery of functional proteins into the cytosol and nucleus. This expands the potential of protein therapeutics beyond lysosomal storage diseases and supports Permeasis’ broader vision of developing intracellular biologics for diseases that have remained out of reach for conventional therapeutic approaches.”
The study was authored by Prabhat Bhat, PhD, who conducted much of the foundational work as a graduate student in Pei’s laboratory and now serves as a consultant to Permeasis.
The underlying technology is covered by patent applications filed by the Ohio State Innovation Foundation and exclusively licensed to Permeasis.
