Sakurai Fuminori
Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Ibaragi City, Japan.
Yakugaku Zasshi. 2008 Dec;128(12):1751-61. doi: 10.1248/yakushi.128.1751.
Properties of gene delivery vehicles, including gene transfer efficiencies and toxicities, are a key parameter for successful gene therapy. Among various types of gene delivery vehicles that have been developed so far, adenovirus (Ad) vectors have promising potentials as a vector for gene therapy because they can easily be grown to high titers and can efficiently deliver genes to both dividing and non-dividing cells. However, recent studies demonstrated some drawbacks of conventional Ad vectors, which are composed of subgroup C Ad serotype 5 (Ad5). First, Ad5 vectors poorly transduce cells lacking the primary receptor for Ad5, coxsackievirus and adenovirus receptor (CAR). Second, majority of adults have neutralizing antibodies to Ad5. In order to overcome these drawbacks, we developed a novel Ad vector which is fully composed of subgroup B Ad serotype 35 (Ad35). Ad35 vectors can infect a variety of human cells because the primary receptor for Ad35, CD46, is ubiquitously expressed in human cells. Furthermore, Ad35 vectors efficiently transduce in the presence of anti-Ad5 antibodies, and seroprevalence of Ad35 in adults is much lower than that of Ad5. In the current review, I introduce our recent work on development and evaluation of Ad35 vectors, and I also discuss the potential of Ad35 vectors as gene delivery vehicles.
基因传递载体的特性,包括基因转移效率和毒性,是成功进行基因治疗的关键参数。在迄今为止开发的各种类型的基因传递载体中,腺病毒(Ad)载体作为一种基因治疗载体具有很大的潜力,因为它们可以很容易地培养到高滴度,并且能够有效地将基因传递到分裂细胞和非分裂细胞中。然而,最近的研究表明传统Ad载体存在一些缺点,这些传统Ad载体由C亚组5型腺病毒血清型(Ad5)组成。首先,Ad5载体很难转导缺乏Ad5主要受体——柯萨奇病毒和腺病毒受体(CAR)的细胞。其次,大多数成年人对Ad5具有中和抗体。为了克服这些缺点,我们开发了一种新型Ad载体,它完全由B亚组35型腺病毒血清型(Ad35)组成。Ad35载体可以感染多种人类细胞,因为Ad35的主要受体CD46在人类细胞中普遍表达。此外,Ad35载体在存在抗Ad5抗体的情况下能有效转导,并且Ad35在成年人中的血清阳性率远低于Ad5。在本综述中,我介绍了我们最近关于Ad35载体开发和评估的工作,并且我也讨论了Ad35载体作为基因传递载体的潜力。