GFP Adeno-Associated Virus ( AAV-ESGLSQS )

As with nearly all other gene therapy vectors, the tropism of AAV-2-derived vectors limits their use for gene transduction in certain tissues, especially when the vectors are delivered systemically. This problem can be partially circumvented by using an AAV serotype whose in vivo gene transduction pattern best matches the application requirements. In addition, the tropism of the AAV capsid can be altered by incorporating a portion of the natural serotype diversity. Alternatively, peptides that mediate binding to the target cell type can be identified by random phage display library screening and then introduced into regions of the AAV capsid that are critical for receptor binding. Insertion of such peptides or other mutational manipulation of the heparin binding domain near position R588 of the VP capsid protein can eliminate the natural tropism of the AAV-2 capsid for cells expressing heparan sulfate proteoglycans (HSPGs) and result in off-targeting of the liver in vivo. AAV-ESGLSQS stands out through its specialized capsid engineering. This involves the careful insertion of the peptide sequence ESGLSQS at position I588 of the AAV2 capsid. The insertion at I588 is a strategically chosen site that allows the virus to maintain its structural integrity while enhancing its ability to target specific cell types. The primary target of AAV-ESGLSQS is tumor cells, making this virus a valuable tool for cancer research. The engineered capsid enables the virus to seek out and bind to tumor cells with greater specificity and efficiency. This specificity is critical in both research and potential therapeutic settings as it reduces off-target effects and maximizes impact on malignant cells.