Vandenberghe Luk H, Wilson James M
Gene Therapy Program, Department of Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Gene Ther. 2007 Oct;7(5):325-33. doi: 10.2174/156652307782151416.
The first in vivo adeno-associated viral vector (AAV) gene transfer experiments were performed in murine models of muscle directed gene transfer. These studies were remarkable for stable expression of a variety of immunogenic transgenes. These findings were translated to other target organs with multiple therapeutic gene products. Technological improvements and the lessons learned from basic research have heralded an era of first-in-human clinical trials. In most settings, AAV appears to evade host immune surveillance, allowing the delivery of robust levels of genetic cargo that leads to persistent expression. However, in few experimental settings immunological responses raised following AAV mediated gene transfer have compromised vector efficacy. Parameters that determine these occurrences have been proposed to be pre-existing immunity to AAV, the route of administration, the kinetics of expression, the dose, the vector serotype and its ability to transduce antigen-presenting cells (APCs) as well as the host species and nature of the specific transgene product. Overall, the underlying mechanisms remain the topic of scientific debate. This review aims to compile, confront and critically discuss the findings in which AAV appears to be an immunogen.
首次体内腺相关病毒载体（AAV）基因转移实验是在肌肉定向基因转移的小鼠模型中进行的。这些研究以多种免疫原性转基因的稳定表达而引人注目。这些发现已转化到使用多种治疗性基因产物的其他靶器官。技术进步以及从基础研究中吸取的经验教训开创了首次人体临床试验的时代。在大多数情况下，AAV似乎能逃避宿主免疫监视，从而能够递送大量的遗传物质并实现持续表达。然而，在少数实验情况下，AAV介导的基因转移后引发的免疫反应会损害载体的功效。据推测，决定这些情况发生的参数包括对AAV的预先存在的免疫力、给药途径、表达动力学、剂量、载体血清型及其转导抗原呈递细胞（APC）的能力，以及宿主物种和特定转基因产物的性质。总体而言，其潜在机制仍是科学争论的话题。本综述旨在汇编、对比并批判性地讨论AAV似乎作为一种免疫原的相关研究结果。
