Suerth Julia D, Labenski Verena, Schambach Axel
Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Viruses. 2014 Dec 5;6(12):4811-38. doi: 10.3390/v6124811.
Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally discovered as cancer-causing agents, have a more random and potentially safer integration pattern compared to gammaretro- and lentiviruses. In this review, we provide a short overview of the history of alpharetroviruses and explain how they can be converted into state-of-the-art gene delivery tools with improved safety features. We discuss development of alpharetroviral vectors in compliance with regulatory requirements for clinical translation, and provide an outlook on possible future gene therapy applications. Taken together, this review is a broad overview of alpharetroviral vectors spanning the bridge from their parental virus discovery to their potential applicability in clinical settings.
使用整合型逆转录病毒载体的基因治疗已在多项治疗遗传性疾病和癌症的临床试验中证明了其有效性。然而，也观察到了与插入诱变相关的载体介导的不良事件，这凸显了对更安全治疗载体的需求。矛盾的是，最初被发现为致癌因子的α逆转录病毒，与γ逆转录病毒和慢病毒相比，具有更随机且可能更安全的整合模式。在本综述中，我们简要概述了α逆转录病毒的历史，并解释了如何将它们转化为具有改进安全特性的先进基因递送工具。我们讨论了符合临床转化监管要求的α逆转录病毒载体的开发，并对未来可能的基因治疗应用进行了展望。综上所述，本综述广泛概述了α逆转录病毒载体，跨越了从其亲本病毒发现到其在临床环境中潜在适用性的桥梁。
