Enhanced cellular uptake of biotinylated antisense oligonucleotide or peptide mediated by avidin, a cationic protein

Abstract
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 bacterial 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 K i or 5 μg/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.