Therapeutic Potential of Nucleic Acid-Based Drugs in Coronary Hyper- Proliferative Vascular Diseases

G.      Grassi; B.      Scaggiante; B.      Dapas; R.      Farra; F.      Tonon; G.      Lamberti; A.      Barba; S.      Fiorentino; N.      Fiotti; F.      Zanconati; M.      Abrami; M.      Grassi

doi:10.2174/09298673113209990031

Abstract

The thickening of the vessel wall (intimal hyperplasia) is a pathological process which often follows revascularization approaches such as transluminal angioplasty and artery bypass graft, procedures used to re-vascularize stenotic artery. Despite the significant improvements in the treatment of intimal hyperplasia obtained in the last years, the problem has not completely solved. Nucleic acid based-drugs (NABDs) represent an emergent class of molecules with potential therapeutic value for the treatment of intimal hyperplasia.

NABDs of interest in the field of intimal hyperplasia are: ribozymes, DNAzymes, antisense oligonucleotides, decoy oligonucleotides, small interfering RNAs and micro interfering RNAs. These molecules can recognize, in a sequencespecific fashion, a target which, depending on the different NABDs, can be represented by a nucleic acid or a protein. Upon binding, NABDs can down-modulate the functions of the target (mRNA/proteins) and thus they are used to impair the functions of disease-causing biological molecules.In spite of the great therapeutic potential demonstrated by NABDs in many experimental model of intima hyperplasia, their practical use is hindered by the necessity to identify optimal delivery systems to the vasculature.

In the first part of this review a brief description of the clinical problem related to intima hyperplasia formation after revascularization procedures is reported. In the second part, the attention is focused on the experimental evidences of NABD therapeutic potential in the prevention of intimal hyperplasia. Finally, in the third part, we will describe the strategies developed to optimize NABD delivery to the diseased vessel.

Keywords: Antisense oligonucleotides, CBG, decoy oligonucleotides, delivery, DNAzymes, intima hyperplasia, micro interfering RNAs, PTA, ribozymes, small interfering RNAs.