Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives

Abstract

The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov).

Fig 1

Genetic molecular targets in ischemic heart disease. (c-Myc = proto-oncogene protein; DEL-1 = developmental endothelial locus 1; eNOS = endothelial nitric oxide synthase; E2F = transcription factor; FGF = fibroblast growth factor; HGF = hepatocyte growth factor; HIF-1α = hypoxia inducible factor 1α; MAPK = mitogen-activated protein kinase; MMP = matrix metalloproteinases; NFAT = nuclear factor of activated T cells; NO = nitric oxide; Oral 1/3 = ORAI calcium release-activated calcium modulator 1/3; SERCA2a = sarcoplasmic reticulum adenosine triphosphatase isoform 2a; SMC = smooth muscle cells; STIM-1 = stromal interaction molecule-1; TIMP = tissue inhibitor metalloproteinases; VEGF = vascular endothelial growth factor.)

Fig 2

Genetic molecular targets in heart failure. (Akt = serine/threonine kinase; βARKct = βAR kinase carboxy terminus; Bcl-2 = B-cell lymphoma; GRK = G-protein-coupled receptor kinase; HO-1 = heme oxygenase enzyme-1; HSP = heat shock protein; P13 = phosphoinositide 3-kinase; ROS = reactive oxidative species; S100A1 = S100 calcium-binding protein A1; SDF-1 = stromal-derived factor 1; SERCA2a = sarcoplasmic reticulum adenosine triphosphatase isoform 2a; TGF-β = transforming growth factor; TNF = tumor necrosis factor.)