Recent Advances in Gene Therapy for Cardiac Tissue Regeneration

Abstract

Cardiovascular diseases (CVDs) are responsible for enormous socio-economic impact and the highest mortality globally. The standard of care for CVDs, which includes medications and surgical interventions, in most cases, can delay but not prevent the progression of disease. Gene therapy has been considered as a potential therapy to improve the outcomes of CVDs as it targets the molecular mechanisms implicated in heart failure. Cardiac reprogramming, therapeutic angiogenesis using growth factors, antioxidant, and anti-apoptotic therapies are the modalities of cardiac gene therapy that have led to promising results in preclinical studies. Despite the benefits observed in animal studies, the attempts to translate them to humans have been inconsistent so far. Low concentration of the gene product at the target site, incomplete understanding of the molecular pathways of the disease, selected gene delivery method, difference between animal models and humans among others are probable causes of the inconsistent results in clinics. In this review, we discuss the most recent applications of the aforementioned gene therapy strategies to improve cardiac tissue regeneration in preclinical and clinical studies as well as the challenges associated with them. In addition, we consider ongoing gene therapy clinical trials focused on cardiac regeneration in CVDs.

Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes

“… 36 , 37 In addition, gene therapy using viral vectors has also been applied to treat atherosclerosis, hyperlipidemias, peripheral ischemia, and arrhythmias. 33 , 38–41 However, viral vectors stimulate inflammatory and immune responses, which raise safety concerns. Furthermore, the therapeutic efficacy of this approach remains a challenge in the heart tissue.…”

A Review of Genes Involved in Wound Healing

“…Closing the external surface of the wound with a new epidermis is the main function of keratinocytes. In the third phase of wound healing, originally, granulation tissue will be transferred to the scar tissue, then the evidence of the successive layers of collagen will be seen, and the scar will be remodeled, typically going on a few months ( 15 , 16 ).…”

The Angiogenic Balance and Its Implications in Cancer and Cardiovascular Diseases: An Overview

“…Although not yet implemented in clinical practice, data gathered in more than 20 years of preclinical and clinical studies has brought great insights and advancement in this field [ 138 , 139 ]. Several clinical trials investigating the effect of different gene therapies on cardiac regeneration are currently ongoing [ 140 ].…”