Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Curr Opin Immunol. 2012 Oct;24(5):592-7. doi: 10.1016/j.coi.2012.08.006. Epub 2012 Sep 14.
Retroviral vectors are unique in their ability to integrate their genome into the host genome of transduced cells. Several members of the retrovirus family show distinct pattern for preferential integration into the host genome. Despite many years of investigation, precise mechanisms of target site selection and the fundamental interplay of viral integrase and host cell proteins are still unknown. Improved methods to detect retroviral integrations genome-wide as well as recent advances on the retroviral integrase structure and integrase interacting proteins may lead to further uncover the process of retroviral target site selection. A better knowledge of these mechanisms and interactions will allow further improving safety of retroviral vectors for gene therapy by providing an opportunity to retarget retroviral integration into non-harmful genomic positions.
逆转录病毒载体具有将其基因组整合到转导细胞的宿主基因组中的独特能力。逆转录病毒家族的几个成员表现出优先整合到宿主基因组的特定模式。尽管经过多年的研究,精确的靶位点选择机制以及病毒整合酶和宿主细胞蛋白的基本相互作用仍然未知。改进的方法可以在全基因组范围内检测逆转录病毒整合,以及逆转录病毒整合酶结构和整合酶相互作用蛋白的最新进展,可能会进一步揭示逆转录病毒靶位点选择的过程。更好地了解这些机制和相互作用将通过提供将逆转录病毒整合到非有害基因组位置的机会,进一步提高逆转录病毒载体用于基因治疗的安全性。