Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons
- Equal contributors
1 Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea
2 Center for RNA Research, Institute for Basic Science, Seoul, Korea
3 Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Korea
4 Department of Biological Sciences, Creative Research Initiatives Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea
Molecular Brain 2014, 7:17 doi:10.1186/1756-6606-7-17Published: 11 March 2014
Adeno-associated virus (AAV) vectors can deliver transgenes to diverse cell types and are therefore useful for basic research and gene therapy. Although AAV has many advantages over other viral vectors, its relatively small packaging capacity limits its use for delivering large genes. The available transgene size is further limited by the existence of additional elements in the expression cassette without which the gene expression level becomes much lower. By using alternative combinations of shorter elements, we generated a series of AAV expression cassettes and systematically evaluated their expression efficiency in neurons to maximize the transgene size available within the AAV packaging capacity while not compromising the transgene expression. We found that the newly developed smaller expression cassette shows comparable expression efficiency with an efficient vector generally used for strong gene expression. This new expression cassette will allow us to package larger transgenes without compromising expression efficiency.