AAV PHP.eB-Null

Adeno-associated virus (AAV) is a species of Parvoviridae, with a single-stranded DNA (ssDNA) genome encapsidated by an icosahedral 60-protein capsid. Recombinant AAV (rAAV) vectors are promising delivery vehicles in the field of gene therapy due to their infectivity to both dividing and non-dividing cells and low pathogenicity. In particular, the AAV9 serotype can penetrate the blood-brain barrier (BBB) ​​and transduce the central nervous system (CNS), and is the focus of intensive research for the treatment of neurodegenerative diseases. However, AAV9 has a broad tropism, targeting both non-neuronal and neuronal cells, which limits its application as a CNS-targeted vector. Researchers have used directed evolution to create multiple rAAV vectors with enhanced and selective CNS tropism. Of particular note, the AAV-PHP.B (PHP.B) and AAV-PHP.eB (PHP.eB) variants of AAV9 exhibit highly enhanced CNS tropism and have been widely used in basic research and preclinical gene therapy studies. PHP.B was evolved by inserting seven random amino acids, TLAVPFK, between residues 588 and 589 of viral protein 1 (VP1), which are located at the outermost end of the protruding VR-VIII loop of the capsid. PHP.eB was created by adding two point mutations at residues 587 (A587D) and 588 (Q588G) of PHP.B, which further enhanced tropism for the CNS.