GFP Adeno-Associated Virus ( A588-RGD4CGLS )

The GFP adeno-associated virus (A588-RGD4CGLS) represents a major advancement in the field of virology and gene therapy, demonstrating the innovative use of capsid engineering to improve specificity and efficacy. This engineered virus is based on adeno-associated virus serotype 2 (AAV2), a widely studied vector known for its safety and ability to transduce a variety of cell types. The core of the A588-RGD4CGLS variant is its capsid modification, namely the strategic insertion of the peptide sequence CDCRGDCFC at position I588. This peptide is critical as it confers the ability to specifically target av-integrin-positive tumor cells. av-integrins are cell adhesion molecules that play a crucial role in tumor angiogenesis and metastasis, making them an ideal target for cancer diagnostics and treatment. The modified AAV vectors containing RGD showed significantly different gene transfer characteristics compared to AAV2 vectors with unmodified capsids. This difference was particularly evident when gene delivery experiments were performed using heparan sulfate proteoglycan (HSPG)-negative cell lines. Targeted gene delivery via RGD-integrin interactions also demonstrates that attachment via HSPGs is not required for efficient AAV transduction of cells. In the absence of HSPG-mediated binding, the transduction activity of AAV particles is not affected by attachment via alternative receptors. RGD peptide-containing rAAV vectors may be very useful for treating tumors characterized by defective HSPG expression. Due to their expanded tropism, these novel vectors are able to effectively transduce in vivo, suggesting that they may offer significant therapeutic advantages.