GFP Adeno-Associated Virus ( AAV2-VNSTRLP )

AAV2-VNSTRLP particles are derived from the well-studied AAV serotype 2 (AAV2), known for its relatively broad tissue tropism and safety profile. However, what makes AAV2-VNSTRLP unique is the precise modification of its capsid structure. Specifically, the peptide sequence VNSTRLP has been strategically inserted at amino acid position I588. This engineering modification is intended to alter the tropism of the virus, allowing it to more effectively target cardiomyocytes (precursor cells that give rise to cardiomyocytes). This specificity is critical for research and therapeutic applications related to cardiac disease, where targeted gene delivery to cardiomyocytes can lead to better outcomes in gene therapy, regenerative medicine, and molecular cardiology research. Synthetic cardiac-relevant AAV strains have also been derived from AAV-based combinatorial peptide display libraries. These libraries were generated by inserting random peptide sequences at position R588 of the AAV2 VP template. After intravenous injection of the AAV peptide library into mice, hearts were excised 3 days after injection and superinfected with human adenovirus 5 as organotypic cultures. The replicated AAV strains were further PCR amplified and screened to generate new cardiac-relevant AAV strains. AAV2-VNSTRLP produced 50-100-fold higher transduction of the heart than non-target organs such as the liver and kidney, with preferential transduction. Furthermore, these strains were found to be more potent than wild-type AAV2, the liver-detargeted AV2/R585E mutant, and AAV9 vectors after intravenous injection.