In situ loading of biologics on and tissue redirection of circulating extracellular vesicles with an anchoring nanobody

NEV3, an EV-anchoring nanobody, binds extracellular vesicles from multiple sources and enables in situ loading of diverse proteins, enhancing intracellular delivery in vitro and in vivo.

• Why it matters: Ex vivo EV production, cargo loading, and quality control limit clinical translation, so a modular in vivo method to load therapeutics and redirect EV biodistribution is needed.
• What they did: Using NEV3 identified by phage display, the study shows protein loading onto EVs via fibronectin interactions and tests targeted conjugates, including protein A-NEV3 and anti-transferrin receptor-protein A-NEV3, in vitro and in vivo.
• The result: In systemic lupus erythematosus mice, intravenous protein A-NEV3 significantly reduces circulating IgG and anti-dsDNA antibodies and improves survival with reduced pathologies; in mdx mice it redirects EVs to muscle and alleviates muscle pathologies.