Targeting and engineering long non-coding RNAs for cancer therapy

Michela Coan; Simon Haefliger; Samir Ounzain; Rory Johnson

doi:10.1038/s41576-024-00693-2

Targeting and engineering long non-coding RNAs for cancer therapy

Nat Rev Genet. 2024 Feb 29. doi: 10.1038/s41576-024-00693-2. Online ahead of print.

Authors

Michela Coan^{1

2

3}, Simon Haefliger^{4

5}, Samir Ounzain⁶, Rory Johnson^{7

8

9

10

11}

Affiliations

¹ School of Biology and Environmental Science, University College Dublin, Dublin, Ireland.
² Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Dublin, Ireland.
³ School of Medicine, University College Dublin, Dublin, Ireland.
⁴ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Department for BioMedical Research, University of Bern, Bern, Switzerland.
⁶ HAYA Therapeutics, Lausanne, Vaud, Switzerland.
⁷ School of Biology and Environmental Science, University College Dublin, Dublin, Ireland. rory.johnson@ucd.ie.
⁸ Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Dublin, Ireland. rory.johnson@ucd.ie.
⁹ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. rory.johnson@ucd.ie.
¹⁰ Department for BioMedical Research, University of Bern, Bern, Switzerland. rory.johnson@ucd.ie.
¹¹ FutureNeuro, SFI Research Centre for Chronic and Rare Neurological Diseases, Dublin, Ireland. rory.johnson@ucd.ie.

PMID: 38424237
DOI: 10.1038/s41576-024-00693-2

Abstract

RNA therapeutics (RNATx) aim to treat diseases, including cancer, by targeting or employing RNA molecules for therapeutic purposes. Amongst the most promising targets are long non-coding RNAs (lncRNAs), which regulate oncogenic molecular networks in a cell type-restricted manner. lncRNAs are distinct from protein-coding genes in important ways that increase their therapeutic potential yet also present hurdles to conventional clinical development. Advances in genome editing, oligonucleotide chemistry, multi-omics and RNA engineering are paving the way for efficient and cost-effective lncRNA-focused drug discovery pipelines. In this Review, we present the emerging field of lncRNA therapeutics for oncology, with emphasis on the unique strengths and challenges of lncRNAs within the broader RNATx framework. We outline the necessary steps for lncRNA therapeutics to deliver effective, durable, tolerable and personalized treatments for cancer.

Publication types

Review