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Cited by 41RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

RNA-Targeted Therapies and High-Throughput Screening Methods

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Zhu, Siran, Rooney, Saul, Michlewski, Gracjan·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21082996PMC PMC7216119
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Abstract

RNA-binding proteins (RBPs) are involved in regulating all aspects of RNA metabolism, including processing, transport, translation, and degradation. Dysregulation of RNA metabolism is linked to a plethora of diseases, such as cancer, neurodegenerative diseases, and neuromuscular disorders. Recent years have seen a dramatic shift in the knowledge base, with RNA increasingly being recognised as an attractive target for precision medicine therapies. In this article, we are going to review current RNA-targeted therapies. Furthermore, we will scrutinise a range of drug discoveries targeting protein-RNA interactions. In particular, we will focus on the interplay between Lin28 and let-7, splicing regulatory proteins and survival motor neuron (SMN) pre-mRNA, as well as HuR, Musashi, proteins and their RNA targets. We will highlight the mechanisms RBPs utilise to modulate RNA metabolism and discuss current high-throughput screening strategies. This review provides evidence that we are entering a new era of RNA-targeted medicine.

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  • Several small molecules and antisense oligos that target miRNA biogenesis as well as miRNA mimics are in clinical trials as candidate therapies for diseases such as non-small cell lung cancer, keloid, chronic hepatitis C, cutaneous T-cell lymphoma and Alport's syndrome.

    “Currently several small molecules and antisense oligos that target miRNA biogenesis as well as miRNA mimics themselves are in clinical trials as candidate therapies for diseases such as non-small cell lung cancer, keloid, chronic hepatitis C, cutaneous T-cell lymphoma and Alport's syndrome (Rupaimoole and Slack, 2017;Zhu et al., 2020).”

    From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Zhu et al., 2020

    The Introduction (page unavailable) reports more than 100 ongoing RNA-targeted therapy trials, and the Conclusions (page unavailable) include ASOs, miRNA mimics and small molecules among therapies under clinical or preclinical evaluation. The paper does not establish that several therapies targeting miRNA biogenesis are in clinical trials for the five named diseases; its Conclusions say the discussed small-molecule miRNA regulators need further research before entering clinical studies. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Zhu, S., Rooney, S., & Michlewski, G.
Affiliations
  • University of Edinburgh (GB)
  • Zhejiang University-University of Edinburgh Institute (CN)
Corresponding author
Michlewski, Gracjan
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-04-23
Volume
21
Issue
8
Pages
2996
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21082996
PMC
PMC7216119
OpenAlex
W3019577475
Cited by
41
References
3
Citations by year
2025: 4 · 2024: 2 · 2023: 4 · 2022: 8 · 2021: 19 · 2020: 4
FWCI
0.84
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
University of Edinburgh (Edinburgh Global Research Scholarship, School of Biomedical Sciences Departmental Fund)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RNA-targeted therapeutics, RNA-binding proteins, RNA-protein interactions, RNA metabolism, Lin28, let-7 microRNA, splicing regulation, SMN, HuR, Musashi, high-throughput screening, drug discovery
MeSH terms
Clinical Studies as Topic, Animals, Drug Evaluation, Preclinical, Humans, RNA, Genetic Therapy, Biomarkers, RNA-Binding Proteins, Treatment Outcome, RNA Interference, Targeted Gene Repair, Drug Discovery, High-Throughput Screening Assays, Molecular Targeted Therapy

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