腺相关病毒
载体(分子生物学)
插入突变
遗传增强
转导(生物物理学)
免疫原性
转基因
病毒学
免疫
生物
医学
病毒载体
计算生物学
免疫学
免疫系统
基因
重组DNA
遗传学
基因组
生物化学
作者
Bijay Dhungel,Ian Winburn,Candida da Fonseca Pereira,Kui Huang,Amit Chhabra,John E.J. Rasko
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2024-01-01
卷期号:14 (3): 1260-1288
被引量:1
摘要
Gene therapy holds promise for patients with inherited monogenic disorders, cancer, and rare genetic diseases. Naturally occurring adeno-associated virus (AAV) offers a well-suited vehicle for clinical gene transfer due to its lack of significant clinical pathogenicity and amenability to be engineered to deliver therapeutic transgenes in a variety of cell types for long-term sustained expression. AAV has been bioengineered to produce recombinant AAV (rAAV) vectors for many gene therapies that are approved or in late-stage development. However, ongoing challenges hamper wider use of rAAV vector-mediated therapies. These include immunity against rAAV vectors, limited transgene packaging capacity, sub-optimal tissue transduction, potential risks of insertional mutagenesis and vector shedding. This review focuses on aspects of immunity against rAAV, mediated by anti-AAV neutralizing antibodies (NAbs) arising after natural exposure to AAVs or after rAAV vector administration. We provide an in-depth analysis of factors determining AAV seroprevalence and examine clinical approaches to managing anti-AAV NAbs pre- and post-vector administration. Methodologies used to quantify anti-AAV NAb levels and strategies to overcome pre-existing AAV immunity are also discussed. The broad adoption of rAAV vector-mediated gene therapies will require wider clinical appreciation of their current limitations and further research to mitigate their impact.
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