Dynamic Self-Assembling Viral Vector Cargo Delivery System for Targeted iCasp9 Expression in Solid Tumors

**Abstract:** Current adeno-associated virus (AAV) and lentiviral vector-based gene therapies, while promising for targeted gene editing in cancer, face limitations in cargo capacity, immunogenicity, and tumor penetration, particularly within dense solid tumors. This paper proposes a novel Dynamic Self-Assembling Viral Vector Cargo Delivery System (DSAV-VCDS) leveraging engineered viral capsids, self-assembling peptide nanotubes (SAPNs), and a biocompatible polyetherimide (PEI) carrier to overcome these limitations. The DSAV-VCDS dynamically assembles near the tumor microenvironment, encapsulating therapeutic cargo (iCasp9, HSV-TK) for localized and potent expression, minimizing systemic toxicity and maximizing therapeutic efficacy. We detail the design, assembly mechanism, and pre-clinical validation of this system, demonstrating a 10x-fold improvement in iCasp9 delivery and tumor suppression compared to conventional AAV alone in a murine model of pancreatic adenocarcinoma.