Stable gene transter to the nervous system using a non-primate lentiviral vector

被引:228
作者
Mitrophanous, KA
Yoon, S
Rohll, JB
Patil, D
Wilkes, FJ
Kim, VN
Kingsman, SM
Kingsman, AJ
Mazarakis, ND
机构
[1] Oxford Biomed UK Ltd, Medawar Ctr, Oxford OX4 4GA, England
[2] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England
关键词
lentiviral/retroviral vectors; rabies-G; dUTPase; S2; EIAV; CNS;
D O I
10.1038/sj.gt.3301023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have constructed a non-primate lentiviral vector system based on the equine infectious anaemia virus (EIAV). This system is able to transduce both dividing and non-dividing cells, including primary cultured hippocampal neurons and neurons and glia in the adult rat central nervous system (CNS), at efficiencies comparable with HIV-based vectors. We demonstrate that the only EIAV proteins required for this activity are gag/pol and that the only accessor protein required for vector production is rev. In addition, we show that the pol encoded dUTPase activity that is found in all non-primate lentiviruses is not required. The vectors can be pseudotypes with a range of envelopes including rabies G and MLV 4070A and can be concentrated to high titres. The ability of EIAV to infect mitotically inactive cells makes this vector an attractive alternative to the immunodeficiency viruses for gene therapy.
引用
收藏
页码:1808 / 1818
页数:11
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