GFP Adeno-Associated Virus ( AAV-LS2 )

For clinical gene therapy approaches, efficient and safe target cell-specific vector systems are absolutely necessary. AAV-based vectors have a favorable safety profile due to their low immunogenicity, lack of any associated pathogenicity, and extrachromosomal location. Therefore, AAV vectors, especially those based on serotype 2 (AAV2), have been extensively studied and used in clinical and preclinical studies. However, vectors based on standard recombinant AAV2 (rAAV2) lack the required efficiency for efficient gene transfer into primary human peripheral blood progenitor cells (PBPCs). Advances in vector development by Müller and colleagues now allow the generation of rAAV capsid mutants that provide higher target cell efficiency and specificity. An AAV random peptide library was developed, introducing a 21 bp random oligonucleotide at amino acid 588 (heparin binding region) of the AAV genome, resulting in a variety of AAV capsid mutants with reduced affinity for the primary receptor for the AAV2 heparan sulfate proteoglycan, resulting in potential new tropisms. When the library is screened on target cells, only clones with good binding properties to the target cells will enter the cells, amplify and undergo subsequent screening. Under selection pressure, viruses with efficient gene transfer function dominate, while candidates with lower efficiency disappear. Through this approach, other research groups have developed highly efficient vectors for various target cells (such as vascular endothelial cells, vascular smooth muscle cells, lung cancer, prostate cancer and cardiomyocytes).