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Updated: Jul 1, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Targeting and engineering long non-coding RNAs for cancer therapy
Michela Coan1,2,3, Simon Haefliger4,5, Samir Ounzain6
1School of Biology and Environmental Science, University College Dublin, Dublin, Ireland.
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.
Insights
Long non-coding RNA (lncRNA) therapeutics offer promising cancer treatments by targeting RNA molecules. Advances in technology are overcoming challenges to develop effective, personalized lncRNA cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- RNA therapeutics (RNATx) target diseases using RNA molecules.
- Long non-coding RNAs (lncRNAs) are key regulators of oncogenic networks.
- lncRNAs present unique therapeutic potential and development challenges.
Purpose of the Study:
- Review the emerging field of lncRNA therapeutics for oncology.
- Highlight the strengths and challenges of lncRNAs in RNATx.
- Outline steps for developing effective lncRNA cancer treatments.
Main Methods:
- Review of current advances in genome editing, oligonucleotide chemistry, multi-omics, and RNA engineering.
- Analysis of lncRNA properties relevant to therapeutic development.
- Discussion of the broader RNATx framework.
Main Results:
- lncRNAs offer distinct therapeutic advantages over protein-coding genes.
- Technological advancements are enabling efficient lncRNA drug discovery pipelines.
- Specific strategies are needed to overcome lncRNA development hurdles.
Conclusions:
- lncRNA therapeutics hold significant promise for personalized cancer treatment.
- Further development is required to ensure effective, durable, and tolerable therapies.
- This review provides a roadmap for advancing lncRNA-based oncology treatments.
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