摘要
基于单克隆抗体(mAbs)的治疗是当前治疗免疫紊乱、肿瘤和感染性疾病的最成功方案之一。衍生于腺相关病毒(AAV)的载体对于递送编码mAbs的基因是非常有吸引力的,因为它们允许长期表达,从而减少给药次数。他们也能穿透生物膜障碍如穿透血脑屏障来转换免疫特异性器官里面的细胞。近期AAV相关的动物实验研究证实 了AAV传递足够数目的抗体以对慢性传染性疾病进行有效的免疫保护几个月甚至几年。根据治疗及其进展,治疗成功地用于预防或治疗途径。本文讨论了AAV应用于mAb和免疫黏附素传递的优势和局限性,以及载体设计和抗体工程的近期的研究进展。载体设计的优化能够提高mAbs的动力学及表达水平,而蛋白质工程能够加强转基因产物性质。此外,本文提供了对对包括阿尔茨海默病,肌萎缩性侧索硬化和癌症的慢性疾病的临床前研究以及传染病的详尽综述。
关键词: 单克隆抗体,重组腺相关病毒,抗体传导,慢性感染性疾病,载体设计
Current Gene Therapy
Title:Antibody Delivery Mediated by Recombinant Adeno-associated Virus for the Treatment of Various Chronic and Infectious Diseases
Volume: 16 Issue: 6
关键词: 单克隆抗体,重组腺相关病毒,抗体传导,慢性感染性疾病,载体设计
摘要: Monoclonal antibodies (mAbs) based-therapies are currently one of the most successful strategies to treat immune disorders, cancer and infectious diseases. Vectors derived from adenoassociated virus (AAV) are very attractive to deliver the genes coding the mAbs because they allow long-term expression thus, reducing the number of administrations. They can also penetrate biological barriers such as the blood-brain-barrier to transduce cells localized in immunoprivileged organs. Recent animal studies with AAV have demonstrated the capacity of AAV to deliver sufficient quantity of antibodies to confer an efficient immunoprotection against chronic and infectious diseases for several months to years. The treatment was successfully applied either for prophylaxis or therapeutic use, depending on the disease and its progression. In this review, we discuss the advantages and the limitations of AAV for mAb and immunoadhesin delivery. Recent advances in vector design and antibody engineering are also presented. Optimization of the vector design can improve the kinetic and the level of mAbs expression whereas protein engineering can enhance transgene product properties. Furthermore, an exhaustive review of pre-clinical studies for chronic diseases including Alzheimer disease, amyotrophic lateral sclerosis and cancer is presented as well as for infectious diseases.
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Antibody Delivery Mediated by Recombinant Adeno-associated Virus for the Treatment of Various Chronic and Infectious Diseases, Current Gene Therapy 2016; 16 (6) . https://dx.doi.org/10.2174/1566523217666170102111251
DOI https://dx.doi.org/10.2174/1566523217666170102111251 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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