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Delivery of Modified mRNA in a Myocardial Infarction Mouse Model
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Locked Nucleic Acid AntimiR Therapy for the Heart
Sabine Samolovac1, Rabea Hinkel2
1Deutsches Primatenzentrum GmbH, Göttingen, Germany.
Methods in Molecular Biology (Clifton, N.J.)
|August 30, 2022
Summary
MicroRNAs (miRNAs) show therapeutic potential for heart failure. Anterograde coronary artery delivery using over-the-wire balloons is a promising method for localized miRNA modulation in the left ventricle.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- RNA Therapeutics
Background:
- Coronary heart disease is a leading cause of death, with chronic heart failure developing in 30% of patients post-myocardial infarction.
- Heart failure involves adverse cardiac remodeling, including cardiomyocyte hypertrophy, fibrosis, and capillary rarefaction.
- MicroRNAs (miRNAs) are implicated in cardiovascular diseases and heart failure, presenting potential therapeutic targets.
Purpose of the Study:
- To explore miRNAs as novel therapeutic targets for heart failure.
- To describe a localized delivery method for miRNA modulators to the left ventricle.
- To validate the anterograde coronary artery application procedure in a large animal model.
Main Methods:
- Investigated the role of dysregulated miRNAs in heart failure and cardiovascular diseases.
- Described miRNA inhibitors (e.g., LNA, AntagomiR) for miRNA knockdown.
- Detailed the anterograde application of miRNA modulators via an over-the-wire (OTW) balloon into coronary arteries.
Main Results:
- miRNA modulation offers a therapeutic strategy for heart failure by targeting ischemia/reperfusion injury, fibrosis, and hypertrophy.
- Local, target region-oriented application of miRNA modulators is crucial to maximize therapeutic effects and minimize off-target adverse events.
- The anterograde coronary artery application is a feasible and translatable method for left ventricular miRNA modulation.
Conclusions:
- Anterograde coronary artery delivery of miRNA modulators is an effective and clinically relevant strategy for treating heart failure.
- This methodology, demonstrated in a pig model, is a standard catheter laboratory procedure, facilitating translation to human patients.
- Targeted miRNA therapy holds significant promise for managing adverse cardiac remodeling and improving outcomes in heart failure patients.
Keywords:
AntagomiRAnterograde deliveryHypertrophyInhibitionIschemic heart diseaseLNAOligonucleotidesmiRNA therapyMore Related Videos
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