Philpott Nicola J, Thrasher Adrian J
Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
Hum Gene Ther. 2007 Jun;18(6):483-9. doi: 10.1089/hum.2007.013.
Vectors based on lentiviruses have become potent tools for efficient gene transfer to multiple cell types both in vitro and in vivo. In part this is attributable to the stability of transduction afforded by integration into the target cell genome. However, evidence indicates that episomal forms of the vector can also be harnessed for effective gene expression. Nonintegrating vectors retain the high transduction efficiency and broad tropism of conventional lentiviruses but avoid the potential problems associated with the nonspecific integration of a transgene. In this respect they are particularly useful in postmitotic tissue because the vector genome is not diluted out through cell division. Here we discuss the various mutations that may be introduced into human immunodeficiency virus-based lentiviral vectors to achieve efficient transduction, and the mechanisms by which these vectors are effective. We also discuss their potential application to gene therapy and the treatment of genetic disease.
基于慢病毒的载体已成为在体外和体内将基因高效转移至多种细胞类型的有力工具。部分原因在于整合到靶细胞基因组所带来的转导稳定性。然而，有证据表明载体的游离形式也可用于有效的基因表达。非整合型载体保留了传统慢病毒的高转导效率和广泛嗜性，但避免了与转基因非特异性整合相关的潜在问题。在这方面，它们在有丝分裂后组织中特别有用，因为载体基因组不会因细胞分裂而被稀释。在此，我们讨论为实现高效转导可能引入基于人类免疫缺陷病毒的慢病毒载体的各种突变，以及这些载体发挥作用的机制。我们还讨论了它们在基因治疗和遗传疾病治疗中的潜在应用。
