Control of intracellular delivery of oligonucleotides by signal peptides and genetic expression in human cells.
In the present study, membrane permeability and intracellular localization of oligonucleotide (ODN) conjugated with naturally occurring functional peptides or designed peptide were investigated, as well as antisense properties of them to inhibit of telomerase activities. All conjugate antisense ODNs showed higher membrane permeability and nuclease resistance than natural ODN. Intracellular localization of ODN could be precisely controlled by conjugation with functional peptides. Conjugate antisense ODNs indicated thousand fold higher inhibitory effects than natural ODN in cellular extract and 95% suppression in human leukemia cells.
Kubo
Takanori
T
Department of Biological and Environmental Chemistry, School of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka 820-8555, Japan.
Kanno
Ken-ichi
K
Ohba
Hideki
H
Rumiana
Bakalova
B
Fujii
Masayuki
M
D001483:Base Sequence; D002457:Cell Extracts; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D021382:Protein Sorting Signals; D019098:Telomerase / Q000037:antagonists & inhibitors
D002457:Cell Extracts; D016376:Oligonucleotides, Antisense; D021382:Protein Sorting Signals; D019098:Telomerase