Division of Neurology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Biomed Res Int. 2013;2013:974819. doi: 10.1155/2013/974819. Epub 2013 May 20.
Recombinant adeno-associated virus (AAV) vectors are powerful tools for both basic neuroscience experiments and clinical gene therapies for neurological diseases. Intravascularly administered self-complementary AAV9 vectors can cross the blood-brain barrier. However, AAV9 vectors are of limited usefulness because they mainly transduce astrocytes in adult animal brains and have restrictions on foreign DNA package sizes. In this study, we show that intracardiac injections of tyrosine-mutant pseudotype AAV9/3 vectors resulted in extensive and widespread transgene expression in the brains and spinal cords of adult mice. Furthermore, the usage of neuron-specific promoters achieved selective transduction of neurons. These results suggest that tyrosine-mutant AAV9/3 vectors may be effective vehicles for delivery of therapeutic genes, including miRNAs, into the brain and for treating diseases that affect broad areas of the central nervous system.
重组腺相关病毒（AAV）载体是基础神经科学实验和神经疾病临床基因治疗的有力工具。血管内给予的自互补 AAV9 载体可以穿透血脑屏障。然而，AAV9 载体的用途有限，因为它们主要转导成年动物大脑中的星形胶质细胞，并且对外源 DNA 包装大小有限制。在这项研究中，我们表明，心脏内注射酪氨酸突变假型 AAV9/3 载体可导致成年小鼠大脑和脊髓中广泛的转基因表达。此外，神经元特异性启动子的使用实现了神经元的选择性转导。这些结果表明，酪氨酸突变的 AAV9/3 载体可能是将治疗基因（包括 miRNA）递送到大脑中以及治疗影响中枢神经系统广泛区域的疾病的有效载体。
