Cited by 4,741MicroRNA in disease regulationRNA Interference and Gene DeliveryCancer-related molecular mechanisms research

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

Rupaimoole, Rajesha, Slack, Frank J.·2017·Nature Reviews Drug Discovery

Abstract

In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

Integrity signals

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Crossref · 10.1038/nrd.2016.246

Cites

194 of 194 references verified0 citation errors · 0 not checkable

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  • Regulation via miRNA-mediated repression of gene expression is involved in nearly every physiological system and misregulation of miRNA biology is implicated in a broad spectrum of diseases.

    “Regulation via miRNA-mediated repression of gene expression has been shown to be involved in nearly every physiological system and misregulation of miRNA biology has been implicated in a broad spectrum of diseases ranging from cancer to neurodegenerative diseases (Quinlan et al., 2017;Rupaimoole and Slack, 2017).”

    From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Rupaimoole and Slack, 2017

  • Dysregulation of miRNA is closely associated with various disease statuses.

    “Studies have identified that the dysregulation of miRNA is closely associated with various disease statuses.[237, 238]”
  • MRG-201 is a synthetic miRNA mimic of miR-29 designed to reduce the expression of collagen and other scar formation related proteins.

    “MRG-201 is a synthetic miRNA mimic of miR-29 designed to reduce the expression of collagen and other scar formation related proteins.[238, 241]”
  • Only a small fraction of preclinical miRNA therapeutics have reached phases of clinical development.

    “Although extensive preclinical studies on miRNA therapeutics have been carried out, only a small fraction of them have reached phases of clinical development.[238]”

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Authors
Rupaimoole, R., & Slack, F. J.
Affiliations
Beth Israel Deaconess Medical Center (US)
Corresponding author
Slack, Frank J.
Venue
Nature Reviews Drug Discovery
Published
2017-02-17
Volume
16
Issue
3
Pages
203-222
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W2588025094
Cited by
4,741
References
195
Citations by year
2026: 268 · 2025: 358 · 2024: 425 · 2023: 561 · 2022: 675 · 2021: 787 · 2020: 710 · 2019: 531 · 2018: 309 · 2017: 113
FWCI
46.31
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
miRNA-based therapy, miRNA mimics, antimiRs, cancer, microRNA dysregulation, tumor suppressor microRNA, oncogenic microRNA, miR-34, miR-122, hepatitis, clinical trials, drug delivery, drug target identification
MeSH terms
Animals, Clinical Trials as Topic, Humans, Neoplasms, Genetic Therapy, Disease Management, MicroRNAs

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