AAV PHP.B-Cre-GFP

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. As of July 2020, more than 100 clinical trials using AAV vectors were registered on ClinicalTrials.gov. Of these trials, more than 70% used capsid sequences isolated from AAVs found in nature, with the most commonly used sequences corresponding to AAV serotypes AAV1, AAV2, AAV8, and AAV9. Different AAV serotypes interact with different cell surface glycans and intracellular trafficking receptors, which influence their native cell transduction efficiency and tissue-specific tropism.

Researchers have successfully applied a technique called "AAV display" to develop AAV vectors with non-native receptor binding properties and tissue transduction. One successful application demonstrated by AAV was the identification of AAV9-PHP.B, an engineered vector that differs from AAV9 by the insertion of a 7-amino acid peptide after residue Q588. When injected intravenously into C57BL/6 mice, the presence of this short peptide enabled AAV9-PHP.B to localize to brain microvasculature, cross the blood-brain barrier (BBB), and elicit widespread transduction of neurons and astrocytes throughout the central nervous system (CNS).