Current limitations of gene therapy for rare pediatric diseases: Lessons learned from clinical experience with AAV vectors

IF 1.3 4区医学 Q3 PEDIATRICS Archives De Pediatrie Pub Date : 2023-11-01 DOI:10.1016/S0929-693X(23)00227-0

Antoine Gardin , Giuseppe Ronzitti

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Abstract

Gene therapy using adeno-associated viral (AAV) vectors is a promising therapeutic strategy for multiple inherited diseases. Following intravenous injection, AAV vectors carrying a copy of the missing gene or the genome-editing machinery reach their target cells and deliver the genetic material. Several clinical trials are currently ongoing and significant success has already been achieved with at least six AAV gene therapy products with market approval in Europe and the United States. Nonetheless, clinical trials and preclinical studies have uncovered several limitations of AAV gene transfer, which need to be addressed in order to improve the safety and enable the treatment of the largest patient population. Limitations include the occurrence of immune-mediated toxicities, the potential loss of correction in the long run, and the development of neutralizing antibodies against AAV vectors preventing re-administration. In this review, we summarize these limitations and discuss the potential technological developments to overcome them.

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目前罕见儿科疾病基因治疗的局限性:从AAV载体临床经验中吸取的教训

利用腺相关病毒(AAV)载体进行基因治疗是一种很有前途的治疗多种遗传性疾病的策略。静脉注射后，携带缺失基因拷贝或基因组编辑机制的AAV载体到达靶细胞并传递遗传物质。目前正在进行几项临床试验，至少有六种AAV基因治疗产品已在欧洲和美国获得市场批准，取得了重大成功。尽管如此，临床试验和临床前研究已经发现了AAV基因转移的一些局限性，这些局限性需要得到解决，以提高安全性并使最大的患者群体得到治疗。限制包括免疫介导毒性的发生，长期可能失去纠正，以及针对AAV载体的中和抗体的发展，以防止再次给药。在这篇综述中，我们总结了这些限制，并讨论了克服它们的潜在技术发展。©2023由Elsevier Masson SAS代表法国儿科学会出版。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Archives De Pediatrie 医学-小儿科

CiteScore

2.80

自引率

5.60%

发文量

106

审稿时长

24.1 weeks

期刊介绍： Archives de Pédiatrie publishes in English original Research papers, Review articles, Short communications, Practice guidelines, Editorials and Letters in all fields relevant to pediatrics. Eight issues of Archives de Pédiatrie are released annually, as well as supplementary and special editions to complete these regular issues. All manuscripts submitted to the journal are subjected to peer review by international experts, and must: Be written in excellent English, clear and easy to understand, precise and concise; Bring new, interesting, valid information - and improve clinical care or guide future research; Be solely the work of the author(s) stated; Not have been previously published elsewhere and not be under consideration by another journal; Be in accordance with the journal''s Guide for Authors'' instructions: manuscripts that fail to comply with these rules may be returned to the authors without being reviewed. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. Archives de Pédiatrie is the official publication of the French Society of Pediatrics.