Enhanced cellular uptake of biotinylated antisense oligonucleotide or peptide mediated by avidin, a cationic protein.
The cellular uptake of a model antisense oligonucleotide complementary to 21 bases of the bovine GLUT-1 glucose transporter mRNA and a model vasopressin peptide that were biotinylated, was markedly stimulated by the presence of avidin, a cationic protein. Conversely, the bacteria homologue of avidin, streptavidin, which is a slightly acidic protein, did not facilitate cellular uptake. The avidin-mediated uptake of biotinylated derivatives was competitively inhibited by another cationic protein, protamine, with a Ki of 5 micrograms/ml; was saturable, temperature- and time-dependent; and was associated with endocytosis. The use of the avidin-biotin system provides a new approach to increasing the cellular uptake of antisense oligonucleotides or peptides.
Pardridge
W M
WM
Department of Medicine, UCLA School of Medicine 90024-1682.
Boado
R J
RJ
D000818:Animals; D001360:Avidin / Q000494:pharmacology*; D001483:Base Sequence; D001710:Biotin / Q000378:metabolism; D001921:Brain / Q000098:blood supply*; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology; D013696:Temperature; D014667:Vasopressins / Q000378:metabolism*
D009004:Monosaccharide Transport Proteins; D016376:Oligonucleotides, Antisense; D011479:Protamines; D014667:Vasopressins; D001360:Avidin; D001710:Biotin