Feng Y, Leavitt M, Tritz R, Duarte E, Kang D, Mamounas M, Gilles P, Wong-Staal F, Kennedy S, Merson J, Yu M, Barber J R
Immusol Inc., 10790 Roselle Street, San Diego, California, 92121, USA.
Virology. 2000 Oct 25;276(2):271-8. doi: 10.1006/viro.2000.0536.
CCR-5 is a major cellular coreceptor for R5 strains of HIV-1. Individuals carrying a homozygous 32-base-pair deletion in this gene are apparently healthy and are relatively resistant to HIV-1 infection. Since CCR5 appears to be dispensable for the host, but important for initial HIV-1 infection, CCR5 mRNA is an excellent therapeutic target for inhibiting HIV-1 replication via ribozyme knockout. We report here that hairpin ribozymes are able to reduce cellular CCR5 mRNA and cell surface CCR5 when stably introduced into PM1 cells by transduction with recombinant adenoassociated viral vector. The ribozymes effectively protect the cells from infection by R5 HIV-1 strains or non-syncytium-inducing clinical isolates commensurate with a reduction in CCR5 mRNA. These results suggest a novel gene therapy approach to preventing or slowing the disease progression of HIV-1 infection.
CCR-5是HIV-1 R5毒株的主要细胞共受体。在该基因中携带纯合32个碱基对缺失的个体显然健康，且对HIV-1感染具有相对抗性。由于CCR5似乎对宿主并非必需，但对HIV-1初始感染很重要，因此CCR5 mRNA是通过核酶敲除抑制HIV-1复制的极佳治疗靶点。我们在此报告，通过重组腺相关病毒载体转导将发夹核酶稳定导入PM1细胞时，能够降低细胞CCR5 mRNA和细胞表面CCR5。这些核酶有效保护细胞免受R5 HIV-1毒株或与CCR5 mRNA减少相称的非合胞体诱导临床分离株的感染。这些结果提示了一种预防或减缓HIV-1感染疾病进展的新型基因治疗方法。
