Cardiac splicing as a diagnostic and therapeutic target

Area of Science:

• Cardiovascular Biology
• Molecular Genetics
• Genomics

Background:

• Many patients with cardiomyopathy and arrhythmias do not respond to current treatments, highlighting the need for novel therapeutic targets.
• Alternative splicing plays a critical role in heart function and disease by determining cardiac RNA transcripts and their properties.

Purpose of the Study:

• To review the role of alternative splicing in myocardial health and disease.
• To discuss how technological advancements facilitate the analysis of cardiac isoform expression.
• To explore the potential of targeting alternative splicing for improved diagnosis and therapy of heart conditions.

Main Methods:

• Review of current literature on alternative splicing in cardiovascular disease.
• Discussion of multiomics, long-read, and single-cell sequencing technologies for analyzing cardiac isoform expression.
• Examination of the translational pipeline for splice modulators.

Main Results:

• Genetic variations highlight alternative splicing's crucial role in cardiomyopathy and arrhythmias.
• Technical advances enable detailed analysis of cardiac isoform expression.
• Cardiac splice regulators are identified as potential therapeutic targets.

Conclusions:

• Understanding alternative splicing offers new avenues for treating heart failure and arrhythmias.
• Targeting splice regulators and utilizing advanced sequencing can lead to improved patient care and clinical decision-making.
• A translational pipeline exists to evaluate splice modulators from bench to bedside.