Cellular effects of antisense c-myc oligodeoxynucleotides are delivery dependent

Drug Delivery
E W Koo, E R Edelman

Abstract

Among the transcription factors critical for cell cycle regulation is the proto-oncogene c-myc. The expression of c-myc upon vascular injury and its inhibition by antisense oligodeoxynucleotides have demonstrated the importance of this protein in the control of proliferation for many cell types, including vascular smooth muscle cells. Liposomes can enhance cellular incorporation of antisense oligodeoxynucleotides, but cellular uptake of oligonucleotides in this manner is still suboptimal, and the oligonucleotides are not protected from enzymatic degradation. Physico-chemical modifications of the oligomers must be developed before antisense oligodeoxynucleotides can be considered as a potential gene therapy for many of the human diseases. This study reports on the enhanced cellular incorporation of antisense phosphodiester oligonucleotides when conjugated to lipophilic linkers. Conjugated phosphodiesters of antisense c-myc oligodeoxynucleotides inhibited cultured human aortic smooth muscle cell growth by 47.5 ± 1.0% 4 days following only a 24-h exposure to the conjugated antisense phosphodiester oligonucleotides. Liposome-enhanced, but unconjugated, phosphodiester and phosphorothioate oligonucleotides were less effective (24.4 ±...Continue Reading

References

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Citations

Jul 25, 2000·Antisense & Nucleic Acid Drug Development·R M HudziakP L Iversen
Dec 6, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·I FishbeinG Golomb

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