Value Proposition
· Superior Anti-Inflammatory Potency: This membrane-associated GAS6 demonstrates over 10-fold higher anti-inflammatory activity compared to equivalent amounts of soluble recombinant GAS6 proteins.
· Dual Mechanism of Action: Inhibits pro-inflammatory cytokine production and concurrently stimulates anti-inflammatory responses, enhancing its efficacy for treating inflammation.
· Targetability: Enables targeted delivery through engineered extracellular vesicles (EVs) equipped with targeting ligands (nanobodies, adhesion molecules, or carbohydrates) that can be directed to specific sites of inflammation.
· Combination Platform: Supports co-delivery of additional anti-inflammatory agents (such as therapeutic miRNAs or surface-expressed proteins) to create synergistic combination therapies.
· Broad Clinical Applicability: Potential applications across a wide range of inflammatory and autoimmune conditions, including: graft versus host disease; hepatitis; non-alcoholic steatosis and alcoholic liver disease; psoriasis, inflammatory bowel disease including Crohn's disease or ulcerative colitis; rheumatoid arthritis; juvenile rheumatoid arthritis; osteoarthritis; gout; and various types of acute inflammation.
Unmet Need
· Current anti-inflammatory therapies, such as small molecules (NSAIDs, glucocorticoids) and biologics (monoclonal antibodies), face significant limitations despite improving patient outcomes. These treatments often cause serious side effects, increase infection susceptibility, and target only narrow inflammatory pathways.
· With chronic inflammatory conditions rising globally, there is urgent need for therapies offering broader efficacy with enhanced safety profiles. Functionalized extracellular vesicles represent a promising solution, leveraging naturally secreted cellular vesicles to deliver anti-inflammatory effects with improved biocompatibility.
Technology Description
· GAS6 (Growth Arrest-Specific 6) is a bridging protein produced by cells in the tissue microenvironment that facilitates efferocytosis (the clearance of apoptotic cells by phagocytes). This process is crucial for resolving inflammation and maintaining tissue homeostasis.
· Existing GAS6-based therapies (recombinant protein administration and gene therapy) show limited efficacy because they depend on binding to endogenous phosphatidylserine (PS)-exposing membranes (the ligand that is exposed on the outer membrane of apoptotic cells), constraining their therapeutic potential.
· Researchers at Johns Hopkins have overcome this limitation by engineering EVs functionalized with membrane-bound GAS6 through two approaches:
1. Overexpressing secreted GAS6 that binds to EV surfaces
2. Expressing transmembrane fusion proteins containing functional GAS6 fragments
Stage of Development
· Current efforts are focused on optimizing a cell production platform with GMP compliance.
Data Availability
· Data available upon request.
Publication
Fabiano, M. P., Adamczyk, A. M., Gololobova, O. A., Mazzitelli, I. G., Leicaj, M. L., Grosso, T. M., Pérez, P. S., Alvarez, C. L., Schachter, J., Palmer, S., Sabbione, F., Erra Díaz, F. A., Trevani, A. S., Varas-Godoy, M., Carrera Silva, E. A., Witwer, K. W., & Ostrowski, M. (2025). Plasma extracellular vesicle surface-located GAS6/PROS1 and CD39/CD73 attenuate inflammation. Cell reports, 44(8), 116096. https://doi.org/10.1016/j.celrep.2025.116096
