Prevention of restenosis by gene therapy.
We have developed an efficient vector system based on the liposome for the delivery of oligonucleotides and genes into various organs. The liposome was decorated with fusion proteins of HVJ (Sendai virus) to introduce DNA directly into the cytoplasm and contained DNA and DNA-binding nuclear protein inside the particle to enhance its expression. Using the vector, called HVJ-liposome gene delivery system, we attempted to prevent the neointima formation of vascular walls after balloon injury. Antisense oligonucleotides against PCNA and cdc2 kinase transferred into injured arterial walls by protein-liposomes greatly reduced the message of those genes and inhibited neointima formation of the injured artery for 8 weeks. Moreover, double-stranded oligonucleotides containing the consensus sequence for E2F binding sites inhibited the growth of smooth muscle cells and prevented neointima formation. Finally, c-NOS gene was introduced into injured rat carotid artery by HVJ-liposome, and neointima formation was inhibited by 70% for 2-4 weeks.
Kaneda
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Morishita
R
R
Dzau
V J
VJ
D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics; D016893:Carotid Stenosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence
D004337:Drug Carriers; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2; D016203:CDC2 Protein Kinase