期刊
CYTOTHERAPY
卷 23, 期 12, 页码 1045-1052出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2021.07.013
关键词
adenovirus vector; hepatotoxicity; liver tropism; gene therapy
类别
资金
- National Natural Science Foundation of China [32002259]
- Natural Science Foundation of Henan Province [202300410198]
Adenoviruses are common pathogens in humans and animals, causing various diseases. Despite being widely used in gene therapy, the liver tropism and side effects of AdVs leading to acute hepatotoxicity have limited their clinical application.
Adenoviruses (Ads), common self-limiting pathogens in humans and animals, usually cause conjunctivitis, mild upper respiratory tract infection or gastroenteritis in humans and hepatotoxicity syndrome in chickens and dogs, posing great threats to public health and livestock husbandry. Artificially modified Ads, which wipe out virulence-determining genes, are the most frequently used viral vectors in gene therapy, and some Ad vector (AdV)-related medicines and vaccines have been licensed and applied. Inherent liver tropism enables AdVs to specifically deliver drugs/genes to the liver; however, AdVs are closely associated with acute hepatotoxicity in immunocompromised individuals, and the side effects of AdVs, which stimulate a strong inflammatory reaction in the liver and cause acute hepatotoxicity, have largely limited clinical application. Therefore, this review systematically elucidates the intimate relationship between AdVs and hepatotoxicity in terms of virus and host and precisely illustrates the accumulated understanding in this field over the past decades. This review demonstrates the liver tropism of AdVs and molecular mechanism of AdV-induced hepatotoxicity and looks at the studies on AdV-mediated animal hepatotoxicity, which will undoubtedly deepen the understanding of AdV-caused liver injury and be of benefit in the further safe development of AdVs. (c) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
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