Systemic Delivery of Tyrosine-Mutant AAV Vectors Results in Robust Transduction of Neurons in Adult Mice

被引：42

作者：

Iida, Asako ^{[1
]}

Takino, Naomi ^{[1
]}

Miyauchi, Hitomi ^{[1
]}

Shimazaki, Kuniko ^{[2
]}

Muramatsu, Shin-ichi ^{[1
]}

机构：

[1] Jichi Med Univ, Dept Med, Div Neurol, Shimotsuke, Tochigi 3290498, Japan

[2] Jichi Med Univ, Div Neurosurg, Shimotsuke, Tochigi 3290498, Japan

来源：

BIOMED RESEARCH INTERNATIONAL | 2013年 / 2013卷

基金：

日本学术振兴会;

关键词：

HIGH-EFFICIENCY TRANSDUCTION; GENE-THERAPY; EXPRESSION; MODEL; BRAIN; ASTROCYTES; MUTATIONS; PHENOTYPE; DISEASE; CAPSIDS;

D O I：

10.1155/2013/974819

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页数：8

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