Dose-response resistance to HIV-1/MuLV pseudotype virus ex vivo in a hairpin ribozyme transgenic mouse model

被引:32
作者
Andäng, M [1 ]
Hinkula, J
Hotchkiss, G
Larsson, S
Britton, S
Wong-Staal, F
Wahren, B
Ährlund-Richter, L
机构
[1] Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden
[2] Karolinska Inst, Div Infect Dis, Dept Immunol Microbiol Pathol & Infect Dis, S-14186 Huddinge, Sweden
[3] Karolinska Inst, Clin Res Ctr, S-14186 Huddinge, Sweden
[4] Karolinska Inst, Microbiol & Tumorbiol Ctr, S-17182 Stockholm, Sweden
[5] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[6] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
关键词
D O I
10.1073/pnas.96.22.12749
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have investigated the efficacy of a hairpin ribozyme targeting the 5' leader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cells derived from transgenic or control mice were infected with HIV-1/MuLV pseudotype virus. A significantly reduced susceptibility to infection in ribozyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response between ribozyme expression and viral resistance, with an estimated cut off Value below 0.2 copies of hairpin ribozyme per cell, These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.
引用
收藏
页码:12749 / 12753
页数:5
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