Cellular uptake and intracellular fate of antisense oligonucleotides.
Antisense oligonucleotides with sequences complementary to a given genetic target can enter cells in sufficient quantities to selectively inhibit gene expression. Thus, they have a potential therapeutic use in preventing undesirable gene expression in diseases such as cancer and AIDS. However, it is remarkable that these molecules, which have high molecular weights and are often charged, gain entry to cells at all. In this article, we review the possible mechanisms by which oligonucleotides enter cells and their subsequent intracellular fates. We also discuss current approaches for improving cellular uptake and delivery of antisense nucleic acids to their intended targets.
Akhtar
S
S
Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Juliano
R L
RL