Intravenous injection of AAV-PHP . eB across the blood-brain barrier in the adult mouse for central nervous system gene therapy *

Over the past 20 years, gene therapy has been developed greatly [1]. In particular, recombinant adeno-associated Viruses (rAAV) are commonly used for delivering genes and vaccines. Safety and efficacy have been evaluated in the clinical trials of therapies for different diseases, including Leber’s congenital amaurosis type 2, Duchenne muscular dystrophy, and hemophilia B [2–5]. AAVs are a kind of non-enveloped single-stranded DNA virus classified as a parvovirus, and their replication depends on the presence of adenoviruses or herpes simplex viruses (also called helper viruses) [6]. They can establish a latent infection in different cell types while having no association with any human disease, making them potential vectors for carrying exogenous transgenes. With genetic engineering, genomes as big as 4.7 kilobases can be loaded and inserted in a region flanked by two inverted terminal repeats, rep for AAV replication and cap for structure proteins and helper genes, and therapeutic rAAV can be produced. Variant AAV capsid sequences generate different serotypes, and currently the 11 most common AAV variants (AAV1–AAV11) have been elucidated from human and non-human tissues [7]. Most serotypes show neuron tropism, including AAV1, AAV2, AAV5, and AAV9 [8–10]. These neurotropic viral vectors are promising candidates for the treatment of central nervous system Intravenous injection of AAV-PHP.eB across the blood-brain barrier in the adult mouse for central nervous system gene therapy*