Prospect and progress of gene therapy in treating atherosclerosis.
BACKGROUND
Despite considerable improvements in therapies, atherosclerotic cardiovascular diseases remain the leading cause of death worldwide. Therefore, in addition to current treatment options, new therapeutic approaches are still needed.


METHODS
In this review, novel gene and RNA interference-based therapy approaches and promising target genes for treating atherosclerosis are addressed. In addition, relevant animal models for the demonstration of the efficacy of different gene therapy applications, and current progress toward more efficient, targeted and safer gene transfer vectors are reviewed.


CONCLUSIONS
Atherosclerosis represents a complex multifactorial disease that is dependent on the interplay between lipoprotein metabolism, cellular reactions and inflammation. Recent advances and novel targets, especially in the field of RNA interference-based therapies, are very promising. However, it should be noted that the modulation of a particular gene is not as clearly associated with a complex polygenic disease as it is in the case of monogenic diseases. A deeper understanding of molecular mechanisms of atherosclerosis, further progress in vector development and the demonstration of treatment efficacy in relevant animal models will be required before gene therapy of atherosclerosis meets its clinical reality.
a 1 University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine , Kuopio, Finland +358 403 552 075 ; Seppo.Ylaherttuala@uef.fi.
Annukka M
AM
Kivelä
a 1 University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine , Kuopio, Finland +358 403 552 075 ; Seppo.Ylaherttuala@uef.fi.
Jenni
J
Huusko
a 1 University of Eastern Finland, A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine , Kuopio, Finland +358 403 552 075 ; Seppo.Ylaherttuala@uef.fi.|b 2 Science Service Center , Kuopio, Finland.|c 3 Kuopio University Hospital, Gene Therapy Unit , Kuopio, Finland.
Seppo
S
Ylä-Herttuala
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D034622:RNA Interference / Q000502:physiology; D016896:Treatment Outcome
RNA interference; atherosclerosis; dyslipidemia; gene therapy; vectors; vulnerable plaques