Osteoarthritis (OA) is a spatially heterogeneous disease in which cartilage degeneration occurs in focal lesions with distinct biochemical and mechanical signatures. These features limit the effectiveness of gene therapies that rely on uniform delivery across the joint. In this talk, I will present our work on engineering disease-adaptive and lesion-targeted gene therapy platforms for OA using Matrix-INverse Targeting (MINT) nanoparticles. The MINT approach leverages pathological changes in cartilage matrix composition to selectively enhance nanoparticle penetration, retention, and gene expression within damaged regions. I will discuss how nanoparticle chemistry and surface properties can be tuned to respond to OA severity and lesion-specific microenvironments, enabling spatially precise delivery of nucleic acid therapeutics.

Nitin Joshi

Assistant Professor of Anesthesia

Mass General Brigham, Harvard Medical School