Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul;12(4):e1640.
doi: 10.1002/wrna.1640. Epub 2021 Jan 1.

Artificial miRNAs as therapeutic tools: Challenges and opportunities

Anna Kotowska-Zimmer  1 , Marianna Pewinska  1 , Marta Olejniczak  1
Affiliations
Review

Artificial miRNAs as therapeutic tools: Challenges and opportunities

Anna Kotowska-Zimmer et al. Wiley Interdiscip Rev RNA. 2021 Jul.

Abstract

RNA interference (RNAi) technology has been used for almost two decades to study gene functions and in therapeutic approaches. It uses cellular machinery and small, designed RNAs in the form of synthetic small interfering RNAs (siRNAs) or vector-based short hairpin RNAs (shRNAs), and artificial miRNAs (amiRNAs) to inhibit a gene of interest. Artificial miRNAs, known also as miRNA mimics, shRNA-miRs, or pri-miRNA-like shRNAs have the most complex structures and undergo two-step processing in cells to form mature siRNAs, which are RNAi effectors. AmiRNAs are composed of a target-specific siRNA insert and scaffold based on a natural primary miRNA (pri-miRNA). siRNAs serve as a guide to search for complementary sequences in transcripts, whereas pri-miRNA scaffolds ensure proper processing and transport. The dynamics of siRNA maturation and siRNA levels in the cell resemble those of endogenous miRNAs; therefore amiRNAs are safer than other RNAi triggers. Delivered as viral vectors and expressed under tissue-specific polymerase II (Pol II) promoters, amiRNAs provide long-lasting silencing and expression in selected tissues. Therefore, amiRNAs are useful therapeutic tools for a broad spectrum of human diseases, including neurodegenerative diseases, cancers and viral infections. Recent reports on the role of sequence and structure in pri-miRNA processing may contribute to the improvement of the amiRNA tools. In addition, the success of a recently initiated clinical trial for Huntington's disease could pave the way for other amiRNA-based therapies, if proven effective and safe. This article is categorized under: RNA Processing > Processing of Small RNAs Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action RNA in Disease and Development > RNA in Disease.

Keywords: RNA interference; artificial miRNA; gene therapy; miRNA; shRNA.

PubMed Disclaimer

References

REFERENCES

    1. Aagaard, L., Zhang, J., von Eije, K. J., Li, H., Sœtrom, P., Amarzguioui, M., & Rossi, J. J. (2008). Engineering and optimization of the mir-106b-cluster for ectopic expression of multiplexed anti-HIV RNAs. Gene Therapy, 15(23), 1536-1549. https://doi.org/10.1038/gt.2008.147
    1. Altuvia, Y., Landgraf, P., Lithwick, G., Elefant, N., Pfeffer, S., Aravin, A., Brownstein, M. J., Tuschl, T., & Margalit, H. (2005). Clustering and conservation patterns of human microRNAs. Nucleic Acids Research, 33(8), 2697-2706. https://doi.org/10.1093/nar/gki567
    1. Andersson, M. G., Haasnoot, P. C. J., Xu, N., Berenjian, S., Berkhout, B., & Akusjärvi, G. (2005). Suppression of RNA interference by adenovirus virus-associated RNA. Journal of Virology, 79(15), 9556-9565. https://doi.org/10.1128/JVI.79.15.9556-9565.2005
    1. Ashizawa, T., Öz, G., & Paulson, H. L. (2018). Spinocerebellar ataxias: Prospects and challenges for therapy development. Nature Reviews. Neurology, 14(10), 590-605. https://doi.org/10.1038/s41582-018-0051-6
    1. Auyeung, V. C., Ulitsky, I., McGeary, S. E., & Bartel, D. P. (2013). Beyond secondary structure: Primary-sequence determinants license pri-miRNA hairpins for processing. Cell, 152(4), 844-858. https://doi.org/10.1016/j.cell.2013.01.031

Publication types

LinkOut - more resources