GFP Adeno-Associated Virus ( AAV-LS3 )

For clinical gene therapy approaches, efficient and safe target cell-specific vector systems are absolutely necessary. To date, vector systems used in preclinical and clinical trials for hematopoietic stem cell transduction are almost exclusively retroviral-based and have the potential for insertional mutagenesis. Adeno-associated viruses (AAV) are small (20 nm), non-enveloped, single-stranded DNA parvoviruses. The advantage of rAAV vectors over other vectors is that AAV can rapidly transduce cells and does not require cell division during transduction, which minimizes the in vitro phase and the use of cytokines. This reduces exposure to nonphysiological conditions and preserves stem cell potential. In addition, due to the low integration rate of rAAV vectors, the system is particularly suitable for "hit-and-go" applications that require short-term expression, such as drug and radioresistance gene transfer (MDR1 and SOD) and gene replacement (by homologous recombination) studies, with the advantage of a very low potential for mutagenesis. AAV-LS3 particles are derived from AAV serotype 2 (AAV2), but they contain a uniquely engineered capsid. The hallmark of this engineered capsid is the insertion of the peptide sequence NRTWEQQ at position I588. This sequence was carefully selected and inserted to modify the tropism of the virus, conferring high specificity for specific cell types. These cell types include tumor cells, particularly chronic myeloid leukemia (CML) cells, and CD34+ hematopoietic stem cells.