Richardson J H, Kaye J F, Child L A, Lever A M
University of Cambridge Department of Medicine, Addenbrooke's Hospital, UK.
J Gen Virol. 1995 Mar;76 ( Pt 3):691-6. doi: 10.1099/0022-1317-76-3-691.
Recombinant vectors based on the type 1 human immunodeficiency virus (HIV-1) can be used to deliver genes into cells expressing the HIV receptor, CD4. We have used a transient RNA packaging system to compare the safety and efficacy of HIV-1 vector transduction by wild-type and replication-deficient helper viruses. Helper virus-free vector transfer was consistently achieved when the helper virus gag-pol and env genes were expressed from separate plasmids such that two recombination events were required to form an infectious genome. Other forms of attenuation, such as deletion of the 5' phi region, were inadequate to prevent helper virus transmission. Vector transduction by the wild-type and non-replicating helper viruses occurred with comparable efficiency except in instances where efficient vector RNA expression was dependent upon transactivating factors supplied by the helper virus. These data demonstrate the feasibility of safe gene transfer using HIV-1 vectors.
基于1型人类免疫缺陷病毒(HIV-1)的重组载体可用于将基因导入表达HIV受体CD4的细胞。我们使用了一种瞬时RNA包装系统,比较野生型和复制缺陷型辅助病毒进行HIV-1载体转导的安全性和有效性。当辅助病毒的gag-pol和env基因从单独的质粒表达,从而需要两次重组事件才能形成感染性基因组时,始终能够实现无辅助病毒的载体转移。其他形式的减毒,如5' φ区域的缺失,不足以防止辅助病毒传播。野生型和非复制型辅助病毒进行的载体转导效率相当,除非高效的载体RNA表达依赖于辅助病毒提供的反式激活因子。这些数据证明了使用HIV-1载体进行安全基因转移的可行性。