Division of Infection and Immunity, Medical School of the Royal Free and University College London, London W1T 4JF, UK.
Arch Immunol Ther Exp (Warsz). 2010 Apr;58(2):107-19. doi: 10.1007/s00005-010-0063-4. Epub 2010 Feb 9.
The concept of gene therapy originated in the mid twentieth century and was perceived as a revolutionary technology with the promise to cure almost any disease of which the molecular basis was understood. Since then, several gene vectors have been developed and the feasibility of gene therapy has been shown in many animal models of human disease. However, clinical efficacy could not be demonstrated until the beginning of the new century in a small-scale clinical trial curing an otherwise fatal immunodeficiency disorder in children. This first success, achieved after retroviral therapy, was later overshadowed by the occurrence of vector-related leukemia in a significant number of the treated children, demonstrating that the future success of gene therapy depends on our understanding of vector biology. This has led to the development of later-generation vectors with improved efficiency, specificity, and safety. Amongst these are HIV-1 lentivirus-based vectors (lentivectors), which are being increasingly used in basic and applied research. Human gene therapy clinical trials are currently underway using lentivectors in a wide range of human diseases. The intention of this review is to describe the main scientific steps leading to the engineering of HIV-1 lentiviral vectors and place them in the context of current human gene therapy.
基因治疗的概念起源于 20 世纪中期，被视为一种具有革命性的技术，有望治愈几乎任何分子基础已经明确的疾病。此后，已经开发出了几种基因载体，并且在许多人类疾病的动物模型中已经证明了基因治疗的可行性。然而，直到新世纪初的一项小规模临床试验中，才在儿童中治愈了一种 otherwise fatal 免疫缺陷疾病，才证明了临床疗效。这项首例成功的治疗是通过逆转录病毒疗法实现的，后来因治疗儿童中出现的大量与载体相关的白血病而黯然失色，这表明基因治疗的未来成功取决于我们对载体生物学的理解。这导致了具有更高效率、特异性和安全性的新一代载体的发展。其中包括 HIV-1 慢病毒载体（慢病毒载体），它们在基础和应用研究中越来越多地被使用。目前正在进行人类基因治疗临床试验，使用慢病毒载体治疗多种人类疾病。本文旨在描述构建 HIV-1 慢病毒载体的主要科学步骤，并将其置于当前人类基因治疗的背景下。
