Lentiviral delivery of short hairpin RNAs.

Lentiviral delivery of short hairpin RNAs.
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短发夹RNA的慢病毒输送。

DOI:
10.1016/j.addr.2009.03.004
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发表时间:
2009-07-25
影响因子:
16.1
通讯作者:
Shankar, Premlata
Shankar, Premlata
中科院分区:
医学1区
文献类型:
--
作者:
Manjunath, N.;Wu, Haoquan;Subramanya, Sandesh;Shankar, Premlata

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在发现后不到十年的时间里,RNA干扰介导的基因沉默已经作为一种潜在的治疗方法在许多疾病的临床试验中进行了测试。慢病毒载体提供了一种表达短发夹状RNA(ShRNA)的方法,从而在分裂和非分裂细胞中诱导稳定和长期的基因沉默,因此,正为此目的而进行深入的研究。然而,诱导长期shRNA表达也可以通过诱导非靶向效应和干扰调节细胞基因表达的内源性microRNA(MiRNA)途径而导致毒性。最近,在shRNA载体的设计方面取得了一些进展,以模拟细胞的miRNA加工过程,并以严格调控和可逆的方式表达多个siRNAs以克服毒性。在这篇综述中,我们描述了其中的一些进展,重点介绍了在开发慢病毒shRNA递送策略以对抗病毒感染方面取得的进展。
In less than a decade after discovery, RNA interference-mediated gene silencing is already being tested as potential therapy in clinical trials for a number of diseases. Lentiviral vectors provide a means to express short hairpin RNA (shRNA) to induce stable and long-term gene silencing in both dividing and non-dividing cells and thus, are being intensively investigated for this purpose. However, induction of long-term shRNA expression can also cause toxicities by inducing off target effects and interference with the endogenous micro RNA (miRNA) pathway that regulates cellular gene expression. Recently, several advances have been made in the shRNA vector design to mimic cellular miRNA processing and to express multiplex siRNAs in a tightly regulated and reversible manner to overcome toxicities. In this review we describe some of these advances, focusing on the progress made in the development of lentiviral shRNA delivery strategies to combat viral infections.
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