Translational Progress and Safety Profiles of Gene Silencing Therapies for Hereditary Cardiomyopathies

International Journal of Cardiology | Vol. 17, No. 3, March 2026 | pp. 182–189

DOI: 10.46882/2026/IJC/001844

Review Article

Translational Progress and Safety Profiles of Gene Silencing Therapies for Hereditary Cardiomyopathies

Emily Davis¹, John Smith²

¹ Division of Cardiovascular Medicine, Mayo Clinic, Rochester, USA
² Department of Cardiology, Harvard Medical School, Boston, USA

Abstract:
The clinical management of inherited heart diseases is shifting rapidly from conventional symptom control toward targeted molecular therapeutics. This comprehensive review synthesizes the recent clinical trial data, safety metrics, and delivery challenges associated with gene silencing platforms, specifically small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), in hereditary cardiomyopathies. Mechanistically, these therapies selectively degrade pathogenic messenger RNA transcripts before translation can occur, effectively preventing the production of misfolded or toxic structural proteins in the myocardium. Recent phase 3 data evaluating siRNA treatments for transthyretin amyloid cardiomyopathy (ATTR-CM) demonstrate a sustained, greater than 85% reduction in circulating toxic protein variants following biannual subcutaneous dosing. This reduction correlates strongly with stabilized global longitudinal strain, decreased myocardial stiffness, and a significant drop in all-cause mortality over a 24-month observation window. Despite these clear therapeutic successes, important challenges persist. These include achieving highly selective, long-term myocardial tissue uptake without systemic accumulation, managing localized injection site or infusion reactions, and monitoring for rare off-target hematological disruptions such as transient thrombocytopenia. Additionally, the high costs of production present major socioeconomic barriers to widespread global patient access. Addressing these specific safety protocols, optimization strategies, and distribution systems is crucial before targeted gene silencing can be integrated into regular clinical workflows for hereditary heart disease.

Keywords: Hereditary cardiomyopathy, Gene silencing, Small interfering RNA, Antisense oligonucleotides, Amyloidosis, Molecular therapeutics

Received: December 22, 2025; Revised: January 26, 2026; Accepted: February 12, 2026; Published: March 18, 2026

Citation: Davis E, Smith J. Translational Progress and Safety Profiles of Gene Silencing Therapies for Hereditary Cardiomyopathies. International Journal of Cardiology, 2026; 17(3): 182–189. DOI: 10.46882/2026/IJC/001844

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