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Overexpressing Long Noncoding RNAs Using Gene-activating CRISPR
Published on: March 1, 2019
Working So Hard: Double-Stranded RNAs That Can Perform Both Gene Activation and Gene Silencing.
Virginia Wing-Nam Chiu1, Matthew Lawrence Hammill1, Marwah Elabed1
1Faculty of Science, Ontario Tech University, Oshawa, Canada.
Chembiochem : a European Journal of Chemical Biology
|June 30, 2026
Summary
Small activating RNAs (saRNAs) can both upregulate and downregulate gene expression, similar to small interfering RNAs (siRNAs). Chemical modifications influence RNA activation (RNAa) and RNA interference (RNAi) activities but do not specifically bias one pathway.
Area of Science:
- Molecular Biology
- RNA Therapeutics
- Gene Regulation
Background:
- Double-stranded RNAs (dsRNAs) are versatile tools for modulating protein expression.
- Small activating RNAs (saRNAs) are dsRNAs structurally similar to small interfering RNAs (siRNAs).
- Chemical modifications on dsRNAs impact gene upregulation potency.
Purpose of the Study:
- To investigate if chemically modified saRNAs can mediate gene silencing.
- To determine the effect of modifications on saRNA gene silencing activity.
- To compare saRNA gene silencing with siRNA activity on the STING gene.
Main Methods:
- Synthesized chemically modified saRNAs and duplex variants.
- Utilized an endogenous plasmid system for gene expression modulation.
- Assessed gene silencing and activation activities of saRNAs and siRNAs.
Main Results:
- saRNAs demonstrated both gene activation (RNAa) and gene silencing (siRNA) capabilities.
- Chemical modifications on the guide strand significantly influenced both saRNA and siRNA activities.
- No specific chemical modification was found to exclusively bias saRNAs towards RNAa or RNAi.
Conclusions:
- saRNAs are versatile molecules capable of both gene activation and silencing.
- Chemical modifications play a crucial role in modulating the activity of short RNAs in RNAi and RNAa pathways.
- Further research into chemical modifications can optimize short RNA-based therapeutics.
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