Huang Xiaopei, Yang Yiping
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Hum Gene Ther. 2009 Apr;20(4):293-301. doi: 10.1089/hum.2008.141.
Recombinant viral vectors such as adenovirus and adenovirus-associated virus have been used widely as vehicles for gene therapy applications because of the high efficiency with which they transfer genes into a wide spectrum of cells in vivo. However, enthusiasm for the use of viral vectors in gene therapy has been tempered by significant problems of attendant host cellular and humoral immune responses that limit their safety and efficacy in vivo. Advances in immunology have suggested a crucial role for the innate immune system in the induction of immune responses to viruses. Thus, a better understanding of the mechanisms by which the host's innate immune system recognizes viruses and viral vectors will help in the design of effective strategies to improve the outcome of viral vector-mediated gene therapy. In this review we first discuss our current understanding of innate immune recognition of viruses in general, and then focus on the innate immune responses to viral vectors for gene therapy.
重组病毒载体,如腺病毒和腺相关病毒,因其能高效地将基因导入体内多种细胞,而被广泛用作基因治疗的载体。然而,由于伴随的宿主细胞和体液免疫反应存在重大问题,限制了其在体内的安全性和有效性,人们对在基因治疗中使用病毒载体的热情有所降温。免疫学的进展表明,先天免疫系统在诱导针对病毒的免疫反应中起关键作用。因此,更好地了解宿主先天免疫系统识别病毒和病毒载体的机制,将有助于设计有效的策略,以改善病毒载体介导的基因治疗效果。在本综述中,我们首先讨论目前对病毒先天免疫识别的总体认识,然后重点关注对用于基因治疗的病毒载体的先天免疫反应。