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Complexity of immune responses to AAV transgene products - Example of factor IX

机译：AAV转基因产品的免疫应答的复杂性 - 因子IX的例子

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After two decades of research, in vivo gene transfer with adeno-associated viral (AAV) vectors has now resulted in successful treatments and even cures for several human diseases. However, the potential for immune responses against the therapeutic gene products remains one of the concerns as this approach is broadened to more patients, diverse diseases, and target organs. Immune responses following gene transfer of coagulation factor IX (FIX) for the treatment of the bleeding disorder hemophilia B has been extensively investigated in multiple animal models. Findings from these studies have not only influenced clinical trial design but have broader implications for other diseases. The impact of vector design and dose, as well as target organ/route of administration on humoral and cellular immune responses are reviewed. Furthermore, the potential for tolerance induction by hepatic gene transfer or combination with immune modulation is discussed.
机译：经过二十几十年的研究，在腺癌相关病毒（AAV）的体内基因转移现已导致成功的治疗，甚至对几种人类疾病治愈。 然而，对治疗基因产物的免疫反应的可能性仍然是担心的一个问题，因为这种方法扩大到更多患者，多种疾病和靶器官。 在多种动物模型中广泛研究了对凝血因子IX（固定）进行凝血因子IX（固定）后的免疫应答。 这些研究的结果不仅影响了临床试验设计，而且对其他疾病具有更广泛的影响。 综述了载体设计和剂量的影响，以及靶器官/给药途径对体液和细胞免疫反应的影响。 此外，讨论了肝基因转移或与免疫调节组合的耐受性诱导的潜力。

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