AAV PHP.B-Cre

Adeno-associated virus (AAV) is a member of the Parvoviridae family and was originally discovered in simian adenovirus preparations. It is one of the smallest known viruses (20-25 nm in diameter) and has a non-enveloped capsid. In humans, infection with AAV does not cause any symptoms or disease. The AAV genome consists of linear single-stranded DNA of approximately 4.7 kb in length, containing two long inverted terminal repeats (ITRs) at the ends. Vectors from most AAV serotypes are able to effectively transduce neurons and glial cells in a wide range of central nervous system (CNS) regions in various species, including humans. Direct injection of AAV vectors into brain tissue via the subarachnoid space or cerebral ventricles results in widespread brain transduction, while intravenous injection results in almost no brain transduction, primarily due to the limited ability of AAV to penetrate the blood-brain barrier (BBB). Recently, Deverman et al. reported that AAVPHP.B, an AAV9 capsid variant with a seven amino acid insertion, has improved BBB permeability compared to AAV serotype 9 (AAV9) in mice. The researchers have successfully achieved efficient and specific transduction of cerebellar Purkinje cells by intravenous injection of AAV-PHP.B carrying the Purkinje cell-specific L7-6 promoter, suggesting the promise of intravenous-mediated transgene delivery and expression in specific cell populations within the central nervous system using AAV-PHP.B in combination with cell-type-specific promoters. Thus, in combination with miRNA expression or genome editing techniques, AAV-PHP.B can be used to efficiently knock down or knock out target genes or knock in genes of interest into target genomic loci by intravenous injection. This approach is of great value in basic neuroscience research and also offers the potential for future clinical applications using gene therapy to treat a variety of genetic diseases affecting the brain.