改善腺病毒递送基因和基因产物动力学的方法。

Approaches to improving the kinetics of adenovirus-delivered genes and gene products.

作者信息

Xu Zhi-Li, Mizuguchi Hiroyuki, Sakurai Fuminori, Koizumi Naoya, Hosono Tetsuji, Kawabata Kenji, Watanabe Yoshiteru, Yamaguchi Teruhide, Hayakawa Takao

机构信息

Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Tokyo 158-8501, Japan.

出版信息

Adv Drug Deliv Rev. 2005 Apr 5;57(5):781-802. doi: 10.1016/j.addr.2004.12.010.

DOI:10.1016/j.addr.2004.12.010

PMID:15757761

Abstract

Adenovirus (Ad) vectors have been expected to play a great role in gene therapy because of their extremely high transduction efficiency and wide tropism. However, due to the intrinsic deficiency of their immunogenic toxicities, Ad vectors are rapidly cleared from the host, transgene expression is transient, and readministration of the same serotype Ad vectors is problematic. As a result, Ad vectors are continually undergoing refinement to realize their potential for gene therapy application. Even after 1999, when a patient fatally succumbed to the toxicity associated with Ad vector administration at a University of Pennsylvania (U.S.) experimental clinic, enthusiasm of gene therapists for Ad vectors has not waned. With great efforts from various research groups, significant advances have been achieved through comprehensive approaches to improving the kinetics of Ad vector-delivered genes and gene products.

摘要

腺病毒（Ad）载体因其极高的转导效率和广泛的嗜性，有望在基因治疗中发挥重要作用。然而，由于其免疫原性毒性的内在缺陷，Ad载体在宿主体内会迅速被清除，转基因表达是短暂的，并且再次施用相同血清型的Ad载体存在问题。因此，Ad载体一直在不断改进，以实现其在基因治疗应用中的潜力。即使在1999年一名患者在美国宾夕法尼亚大学的一家实验诊所因与Ad载体给药相关的毒性而不幸死亡之后，基因治疗师对Ad载体的热情也并未消退。在各个研究小组的巨大努力下，通过综合方法改善Ad载体递送基因和基因产物的动力学，已经取得了重大进展。