人造病毒可以定位感染艾滋病病毒细胞

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用激光发射装置标记敌方目标,引导战斗机或轰炸机对其实施精确打击。这是在好莱坞大片中经常可以看到的场景,同时也是现代战争中地空协作的一个经典范例。而日前由美国南加州大学研究人员完成的一项研究,有望让这一战术在人类与艾滋病的战斗中获得应用,实现对艾滋病病毒(HIV)的精确打击。

据美国每日科学网8月9日(北京时间)报道,南加州大学的研究人员日前培育出了一种病毒,其能够作为载体精确定位被HIV病毒感染的细胞。这无疑为艾滋病这个“超级癌症”的治疗带来了无限遐想,相关治疗方法也有望因此获得新突破。

负责该项研究的南加州大学维特比工程学院教授王品(音译)说,由他们培育出的这种慢病毒载体能够定位被HIV病毒感染的细胞,而后可采用“自杀基因疗法”,让后续药物发现并将病毒细胞摧毁。这个过程类似于军事上的“友军激光标记”——即地面战斗人员使用激光发射装置对敌方目标进行标记,而后战斗机在激光的引导下对目标实施精确打击。这种针对艾滋病病毒的慢病毒载体将只对那些被艾滋病病毒感染的细胞进行标记,未被感染的细胞则将完全处于不会受到伤害的“安全区域”,这就避免了治疗所带来的副作用。

“就目前而言,在单独使用的情况下,还没有任何药物能够实现如此‘精确的打击’。如果你能够消灭掉所有被HIV病毒感染的细胞,将最终能够找到解决问题的办法。”王品说。

研究人员介绍说,目前这种慢病毒载体只在培养皿中进行过测试。实验显示,该法单次能够杀灭35%的艾滋病病毒。虽然这一比例并不算高,但在应用于临床时,可将其反复使用数次,以达到最佳疗效。在接下来的步骤中,研究人员将使用这种方法进行小鼠实验。

王品说,虽然这是一个重大的突破,为艾滋病的治疗指明了一条新的路径,但目前这项研究尚处于初级阶段,距离治愈艾滋病还有很长的一段路要走。

该项目由美国国立卫生研究院(NIH)资助,相关论文发表在7月23日出版的《病毒研究》杂志上。

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Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins

Chi-Lin Lee, Jason Dang, Kye-Il Joo and Pin Wang

Lentiviral vectors (LVs) derived from human immunodeficiency virus type 1 (HIV-1) are promising vehicles for gene delivery because they not only efficiently transduce both dividing and non-dividing cells, but also maintain long-term transgene expression. Development of an LV system capable of transducing cells in a cell type-specific manner can be beneficial for certain applications that rely on targeted gene delivery. Previously it was shown that an inverse fusion strategy that incorporated an HIV-1 receptor (CD4) and its co-receptor (CXCR4 or CCR5) onto vector surfaces could confer to LVs the ability to selectively deliver genes to HIV-1 envelope-expressing cells. To build upon this work, we aim to improve its relatively low transduction efficiency and circumvent its inability to target multiple tropisms of HIV-1 by a single vector. We investigated a method to create LVs co-enveloped with the HIV-1 cellular receptor CD4 and a fusogenic protein derived from the Sindbis virus glycoprotein and tested its efficiency to selectively deliver genes into cells expressing HIV-1 envelope proteins. The engineered LV system yields a higher level of transduction efficiency and a broader tropism towards cells displaying the HIV-1 envelope protein (Env) than the previously developed system. Furthermore, we demonstrated in vitro that this engineered LV can preferentially deliver suicide gene therapy to HIV-1 envelope-expressing cells. We conclude that it is potentially feasible to target LVs towards HIV-1-infected cells by functional co-incorporation of the CD4 and fusogenic proteins, and provide preliminary evidence for further investigation on a potential alternative treatment for eradicating HIV-1-infected cells that produce drug-resistant viruses after highly active antiretroviral therapy (HAART).


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