Figure 4.

Strategies for gene therapy in HCM. HCM is mainly caused by dominant mutations in sarcomere genes, with the majority of mutations found in MHY7 or MYBPC3. The mechanisms by which HCM mutations in sarcomere genes cause arrhythmias are incompletely understood. Gene therapy strategies that have been tested to prevent arrhythmias and other HCM phenotypes have included: (1) gene replacement, (2) allele-specific silencing, and (3) modulation of Ca²⁺ signalling pathways. Abbreviations: AON, antisense oligonucleotides; siRNA, small-interfering RNA; GoF, gain-of-function; CaMKII, Ca²⁺/calmodulin-dependent protein kinase II.