Extension of Exosome-Mediated VGF mRNA Delivery: Addressing 3D Organoid Penetration Bottleneck with a Proposed Magnetic-Controlled Silk Fibroin Tadpole Platform

Alzheimer's disease (AD) is characterized by mitochondrial dysfunction and amyloid-beta deposition. In 2025, exosome-mediated delivery of VGF mRNA was shown to significantly improve mitochondrial bioenergetics and electrophysiological activity in SH-SY5Y cells and preliminary iPSC-derived organoids (DCPS Science Fair 11th Grade 2nd Place, Mayo Clinic SPARK Alumnus). However, Aβ42 reduction remained non-significant due to limited 3D penetration (P > 0.05). This continuation project proposes to further extend Yaya’s 2025 validated EV-mediated VGF mRNA delivery results into 3D organoid cross-pathology models and introduces a magnetic-controlled silk fibroin tadpole active delivery system as Phase 2 to address the penetration bottleneck. No new experiments were performed in 2026; this proposal is based on 2025 validated results and is planned for 2027 extension.