AAV PHP.B-Null

Adeno-associated virus (AAV)-based vectors represent the most commonly used gene transfer modality in human gene therapy clinical trials. This trend is largely due to the favorable safety profile of AAV vectors, their ability to transduce both dividing and non-dividing cells, and the long-term gene expression provided by the AAV vector genome in vivo. Different AAV serotypes interact with different cell surface glycans and intracellular trafficking receptors, which influence their native cell transduction efficiency and tissue-specific tropism. While these native AAV serotypes can effectively deliver genetic material to certain organs (e.g., liver) or cell types, delivery to other tissues (e.g., brain, skeletal muscle, or lung) could be improved to expand their therapeutic potential.

Designing a viral vector that penetrates the blood-brain barrier (BBB) ​​after intravenous injection and effectively transduces the mammalian central nervous system is extremely challenging. In 2016, Deverman et al. reported a vector named PHP.B, a capsid variant of AAV serotype 9 (AAV9). PHP.B was isolated using the C57BL/6J mouse strain by screening for capsid variants that cross the BBB following intravenous infusion of a capsid library, each with a different seven amino acid insertion. The discovery of PHP.B has significant implications for scientists and clinicians in the gene therapy field as it holds the promise of delivering therapeutic genes to the human central nervous system via intravenous injection of PHP.B without the need for invasive surgery.