scAAV PHP.S-CAG-GFP

Adeno-associated viruses (AAVs) have been widely used as vectors for gene transfer to the nervous system, enabling gene expression and knockdown, gene editing, circuit regulation, in vivo imaging, disease model development, and evaluation of therapeutic candidates for neurological disorders. AAVs are well suited for these applications because they enable safe and long-term expression in the nervous system. Most of these applications rely on local injection of AAV into the adult brain to bypass the blood-brain barrier (BBB) ​​and restrict transgene expression in time and space. Targeted AAV injections have also been used to deliver genes to peripheral neurons to test strategies for treating chronic pain and to track, monitor, and modulate specific subsets of vagal neurons. Systemic AAV delivery offers a non-invasive alternative for widespread gene delivery to the nervous system. However, the high viral loads required and relatively low transduction efficiencies limit the broad application of this approach. Using a cell-type-specific capsid selection method called CREATE (AAV Targeted Evolution via Cre Recombinase), researchers identified AAV-PHP.B, a capsid that transduces most neurons and astrocytes in many regions of the adult mouse brain and spinal cord following intravenous injection. Next, the AAV9-based 7-mer library was screened separately in GFAP-Cre mice. After two rounds of screening, the researchers discovered a variant. While both the QAVRTSL variant and AAV9 showed similar sparse brain conduction, the QAVRTSL variant appeared to have significant conduction to peripheral sensory afferents entering the spinal cord and brainstem. This variant was designated AAV-PHP.S. The enhanced sensory neuron tropism of AAV-PHP.S may facilitate widespread gene transfer to peripheral nervous system (PNS) cells.