The Challenges of Long-Term Transcriptional Gene Silencing by RNA Viruses

Since the past few decades, the small RNA (sRNA) technologies including small interfering RNA and miRNA have been widely explored for therapeutic development. Classically, these sRNAs target the coding regions of mRNA to exert temporal gene silencing in a post-transcriptional manner. Interestingly,...

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Bibliographic Details
Published in:Trends in biochemical sciences (Amsterdam. Regular ed.) 2018-09, Vol.43 (9), p.649-650
Main Authors: Ma, Xiao-xia, Ma, Zhongren, Pan, Qiuwei
Format: Article
Language:English
Subjects:
challenge
Epigenesis, Genetic
Gene Silencing
MicroRNAs
RNA viral vector
RNA Viruses - genetics
RNA, Small Interfering
transcriptional gene silencing
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Summary:Since the past few decades, the small RNA (sRNA) technologies including small interfering RNA and miRNA have been widely explored for therapeutic development. Classically, these sRNAs target the coding regions of mRNA to exert temporal gene silencing in a post-transcriptional manner. Interestingly, sRNAs targeting gene promoters have been recently described to mediate long-term transcriptional gene silencing (TGS) by epigenetic modifications. This has further harnessed the potential applications in gene therapy. However, efficient delivery is a common hurdle for almost any types of gene therapy approaches. In a recent issue of Trends in Biochemical Sciences, Baltusnikas et al. have proposed to use RNA viruses to deliver sRNA for long-term TGS, suggesting long-term therapy by a single administration approach for various diseases, including chronic, incurable, and fatal illnesses. Being a novel and ambitious gene therapy strategy, we hereby would like to emphasize three major challenges and propose potential solutions.
ISSN:0968-0004
1362-4326
DOI:10.1016/j.tibs.2018.06.010