hSyn-NULL AAV (Serotype PHP.eB)

Adeno-associated virus (AAV) serotype PHP.eB is an engineered viral vector derived from AAV9, exhibiting enhanced central nervous system (CNS) targeting. Its main advantage lies in the introduction of a peptide sequence into the viral capsid, significantly improving its ability to penetrate the blood-brain barrier (BBB) ​​compared to natural serotypes. This modified capsid structure allows for more efficient binding to brain endothelial cells, resulting in significantly widespread transduction throughout the brain and spinal cord after systemic intravenous injection. PHP.eB demonstrates superior neuronal transduction efficiency (typically transducing over 50% of CNS cells) while maintaining the low immunogenicity and good safety profile of AAV vectors. Furthermore, it exhibits less retention in the liver compared to AAV9, allowing for lower therapeutic doses in CNS applications.

The primary application of PHP.eB is in gene therapy for neurological diseases requiring whole-brain transduction, including lysosomal storage disorders, Parkinson''s disease, and Huntington''s disease. It has been successfully used in preclinical studies to deliver therapeutic genes (e.g., the GBA1 gene for Gaucher disease), CRISPR components for gene editing, and optogenetic tools for neuroscience research. Beyond monogenic diseases, PHP.eB also shows potential for treating complex neurodegenerative diseases such as Alzheimer''s disease by delivering antibody fragments. Its ability to transduce astrocytes and microglia extends its applications to neuroinflammatory diseases. Notably, the systemic delivery method of PHP.eB avoids invasive intracranial injections, thus facilitating clinical translation.