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Published on: August 2, 2018
Targeting Circular RNAs (circRNAs) in Atherosclerosis Using CRISPR Technology
Areej Nazarudeen1, V A Aswathy2, Arun A Rauf1
1Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.
Insights
Circular RNAs (circRNAs) and CRISPR gene editing show promise for treating atherosclerosis. Research highlights specific circRNAs and CRISPR-Cas systems for novel therapeutic strategies against cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Gene Editing Technology
Background:
- Atherosclerosis is a major cause of cardiovascular disease, driven by chronic inflammation.
- Circular RNAs (circRNAs) regulate key processes in inflammation, lipid metabolism, and plaque stability relevant to atherosclerosis.
- Specific circRNAs like circANRIL, circHIPK, and circRSF1 are implicated in atherosclerosis development.
Purpose of the Study:
- To review the biogenesis and functions of circRNAs in atherosclerosis.
- To explore the application of CRISPR-Cas technology (Cas9 and Cas13) in studying and potentially treating atherosclerosis.
- To discuss the potential of circRNA-based therapies and CRISPR-Cas13 for atherosclerosis.
Main Methods:
- Review of existing literature on circRNAs and CRISPR-Cas technology in atherosclerosis research.
- Analysis of specific circRNAs (circANRIL, circHIPK, circRSF1) and their roles.
- Examination of CRISPR-Cas9 applications for lipid metabolism modification and CRISPR-Cas13 for RNA-level intervention.
Main Results:
- CRISPR-Cas9 enables targeting genes like PCSK9, LDLR, and APOB to modulate lipid metabolism and treat conditions like familial hypercholesterolemia in atherosclerosis models.
- CRISPR-Cas13 offers a novel RNA-targeting strategy for selective circRNA editing to regulate atherosclerosis-related pathways.
- Specific circRNAs significantly influence atherosclerosis progression and development.
Conclusions:
- CircRNA research and CRISPR innovation hold revolutionary potential for atherosclerosis treatment.
- Further research is needed to elucidate circRNA mechanisms and develop effective CRISPR-Cas13 delivery systems.
- Extensive preclinical validation is crucial to translate these findings into clinical applications for cardiovascular disease.
Abstract:
Atherosclerosis is a chronic inflammatory condition that remains a major global cause of cardiovascular morbidity and death. Circular RNAs (circRNAs), emerging as key regulators of biological processes, have been linked to atherosclerosis because of their functions in inflammation, lipid metabolism, and plaque stability. This review explores the biogenesis and cellular functions of circRNAs, highlighting specific circRNAs, such as circANRIL, circHIPK, and circRSF1, which influence atherosclerosis progressions and development. CRISPR-Cas technology, specifically Cas9 and Cas13, has transformed the way atherosclerosis is studied and potentially treated. Targeting PCSK9, LDLR, and APOB to modify lipid metabolism, including lowering LDL cholesterol and repairing mutations in familial hypercholesterolemia, has been made possible using CRISPR-Cas9 in atherosclerosis models. In parallel, CRISPR-Cas13 offers a novel approach for RNA-level intervention by selectively editing circRNAs, providing a dynamic approach to regulate atherosclerosis-related pathways. In order to convert these findings into therapeutic treatments, future research should focus on elucidating the mechanics of circRNA, which in turn determines CRISPR-Cas13, and designing specific delivery systems. This review paper demonstrates the revolutionary promise of circRNA research and CRISPR innovation in the treatment of atherosclerosis and underscores the need for extensive preclinical validation to bridge the gap towards clinical use.
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