PDF(Pubmed)
Abstract：
Given the increasing number of gene transfer therapy studies either completed or underway, there is growing attention to the importance of preexisting adaptive immunity to the viral vectors used. The recombinant viral vectors developed for gene transfer therapy share structural features with naturally occurring wild-type virus. Antibodies generated against viral vectors obtained through a previous exposure to wild-type virus can potentially compromise transgene expression by blocking transduction, thereby limiting the therapeutic efficacy of the gene transfer therapy; they may also pose potential safety concerns. Therefore, systemic gene transfer delivery requires testing patients for preexisting antibodies. Two different assays have been used: (1) binding assays that focus on total antibodies (both neutralizing and non-neutralizing) and (2) neutralizing assays that detect neutralizing antibodies. In this review we focus on adeno-associated virus-based gene therapies, describing the immune response that occurs to naturally occurring adeno-associated viruses, the implications for patients with this exposure, the assays used to detect preexisting immune responses, and strategies to circumvent preexisting adaptive immunity to expand the patient base that could benefit from such therapies.
摘要：
鉴于越来越多的基因转移治疗研究已经完成或正在进行，人们越来越关注预先存在的适应性免疫对所用病毒载体的重要性。为基因转移疗法开发的重组病毒载体与天然存在的野生型病毒具有相同的结构特征。针对通过先前暴露于野生型病毒而获得的病毒载体产生的抗体可能通过阻断转导而潜在地损害转基因表达。从而限制了基因转移疗法的疗效;它们也可能带来潜在的安全性问题。因此,系统基因转移递送需要检测患者先前存在的抗体.已经使用了两种不同的测定:(1)集中于总抗体(中和非中和)的结合测定和(2)检测中和抗体的中和测定。在这篇综述中，我们专注于基于腺相关病毒的基因治疗，描述了对天然存在的腺相关病毒的免疫反应，这种暴露对患者的影响，用于检测预先存在的免疫反应的检测，以及规避先前存在的适应性免疫的策略，以扩大可能从此类疗法中受益的患者基础。
