GFP Adeno-Associated Virus ( AAV2-TLH )

The future of gene therapy for neurological diseases will depend on the development of safe, efficient, and targeted vectors. The administration of such vectors should be technically simple and the vectors should be able to reach the entire CNS through the circulation, not just limited areas suitable for local application. The ability to cross the blood-brain barrier has long been considered a prerequisite for CNS-directed gene therapy vectors. However, due to the close proximity of neurons and endothelial cells, transduction of CNS-associated endothelium by targeted vectors appears sufficient to induce therapeutic effects in at least some CNS diseases. Several AAV serotypes allow neuronal transduction after local administration, and some of them appear to be able to cross the mature blood-brain barrier after systemic administration in adult animals. GFP adeno-associated virus (AAV2-TLH) is a reporter AAV vector that has been engineered and modified with the capsid to enhance its specific targeting and transduction efficiency within the central nervous system (CNS). AAV2-TLH particles differ from native AAV2 primarily by the insertion of the peptide sequence GWTLHNK at position I587 of the viral capsid. Insertion of the peptide GWTLHNK confers enhanced properties to the AAV2 capsid, including the potential for improved binding affinity to receptors ubiquitous in central nervous system tissues.