# Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction

## TL;DR

This review explores how gene therapy targeting mitochondria could help treat heart failure by improving energy production in heart cells.

## Contribution

The paper highlights the potential of adeno-associated virus-based gene therapy to address mitochondrial dysfunction in heart failure.

## Key findings

- Mitochondrial dysfunction in heart failure is linked to energy production shifts and oxidative stress.
- AAV vectors offer a promising method to deliver genes and restore mitochondrial function in cardiomyocytes.
- Gene therapy could modulate mitochondrial biodynamics and reduce oxidative stress in heart failure.

## Abstract

Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise specified. Mitochondrial dysfunction, a distinctive feature of HF, leads to a progressive decrease in bioenergetic reserves due to switching of energy production from oxidation of fatty acids in mitochondria to glycolytic pathways. The main problem in developing methods to improve mitochondrial function lies in the fact that protein preparations injected through the bloodstream cannot enter cells through the plasma membrane. Modern gene therapy involving the delivery of missing genes to cells using adeno-associated virus (AAV) vectors has the potential to improve the function of cardiomyocytes (CMCs). This type of therapy aims to target proteins that have been lost, damaged, or altered due to pathological conditions in the myocardium. This review summarizes pathophysiological mechanisms associated with mitochondrial dysfunction, which is mainly caused by increased oxidative stress and impaired mitochondrial biodynamics under HF progression. It also addresses possible ways to modulate these processes using gene therapy. Special attention is paid to modern characteristics of AAVs that can be used as vectors for the efficient delivery of desired genes to CMCs.