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Updated: Sep 13, 2025

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Structure-function-guided drug development efforts to target lncRNAs
Hollie Watmuff1, Amy Crawford1, Bryan Eusse1
1Department of Chemistry, New York University, 31 Washington Place, New York, NY, USA.
Abstract:
Long noncoding RNAs (lncRNAs) play a pivotal role in regulating cellular processes, and their dysregulation has been linked to the progression of disease. Understanding the structural characteristics, protein interactions, and expression dynamics of lncRNAs is essential for deciphering their functional mechanisms. Recent advancements in structural probing techniques have unveiled critical structural motifs and RNA-protein interfaces that contribute to lncRNA dysfunction. Furthermore, developing small molecules, antisense oligonucleotides, and peptidomimetic-based therapeutic agents that target these motifs and interfaces presents promising strategies for treating lncRNA-mediated diseases. This review provides fresh insights into how lncRNAs contribute to disease pathogenesis, focusing on well-characterized lncRNAs, including MALAT1, HOTAIR, GAS5, NEAT1, and XIST as case studies, and explores potential therapeutic agents targeting these lncRNAs to support future drug development efforts.
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