艾滋病基因疗法动物实验获成效

来源: TBz 于 2011-12-02 16:47:39 [档案] [博客] [旧帖] [给我悄悄话] 本文已被阅读：次 (16128 bytes)

在“世界艾滋病日”到来之际，英国《自然》杂志网站11月30日刊登研究报告说，美国研究人员探索出的一种艾滋病基因疗法在动物实验中取得成效。实验证明感染大剂量艾滋病病毒的实验鼠也可受到保护。

美国加州理工学院等机构的研究人员报告说，通过使用一种经过改造的腺病毒，可以在实验鼠肌肉细胞的基因序列中加入一段代码，使得肌肉细胞能够生成和分泌一些抗体。这些抗体具有帮助机体抑制艾滋病病毒的作用，最初是在一些对艾滋病有抵抗力的患者体内分离得到的。

研究人员用这种基因疗法测试了5种不同抗体的效果，结果发现，两种代号为B12和VRC01的抗体效果尤其良好。即使对实验鼠施加比天然感染艾滋病所需病毒量高出100倍的病毒剂量，这两种抗体也能起到完全且持续的保护效果，实验鼠在接受治疗一年后仍能避免发病。这是因为实验鼠的肌肉细胞在基因序列被改变后，会持续生成相关抗体并释放到血液中。

参与研究的戴维·巴尔的摩说，动物实验的成功为接下来开展人类临床试验铺平了道路。虽然通常只用基因疗法治疗遗传病，但目前在与艾滋病的斗争中还没找到完全有效的疗法，因此基因治疗艾滋病值得一试。

据介绍，这种疗法可能导致相关细胞的基因序列永久性改变，或许会带来副作用。研究人员希望能在临床试验中确定该基因疗法是否有副作用并找到规避方法。（来源：新华网黄堃）

Antibody-based protection against HIV infection by vectored immunoprophylaxis

Nature

(2011)

doi:10.1038/nature10660

Received: 25 July 2011
Accepted: 21 October 2011
Published online: 30 November 2011

Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains^{1, 2, 3, 4, 5}. These antibodies all exhibit an unusually high level of somatic mutation⁶, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen⁷. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes^8, 9, 10, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.