Development of Optimized AAV Serotype Vectors for High-Efficiency Transduction at Further Reduced Doses

作者：Ling Chen^*; Li Baozheng; Ma Wenqin; Srivastava Arun

来源：Human Gene Therapy Methods, 2016, 27(4): 143-149.

DOI：10.1089/hgtb.2016.054

We have described the development of capsid-modified next-generation AAV vectors for both AAV2 and AAV3 serotypes, in which specific surface-exposed tyrosine (Y), serine (S), threonine (T), and lysine (K) residues on viral capsids were modified to achieve high-efficiency transduction at lower doses. We have also described the development of genome-modified AAV vectors, in which the transcriptionally inactive, single-stranded AAV genome was modified to achieve improved transgene expression. Here, we describe that combination of capsid modifications and genome modifications leads to the generation of optimized AAV serotype vectors, which transduce cells and tissues more efficiently, both in vitro and in vivo, at similar to 20-30-fold reduced doses. These studies have significant implications in the potential use of the optimized AAV serotype vectors in human gene therapy.

• 出版日期2016-8