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Abstract
We have employed chemical modification strategies to improve cellular ahsorption of oligonucleotides. These include the conjugation of various pendant moieties to the oligonucleotide to affect its overall physical properties such as hydrophobicity, charge, and amphipathicity as well as pendants that may mediate absorption by binding to certain cellular receptors which internalize specific ligands. Our laboratory has prepared polyamines, polyethylene glycols and lipidic constituents conjugated to oligonucleotidcs in order to study their effects in enhancing absorption of antisense agents. These conjugates were targeted against human or murine Intercellular Adhesion Molecule- 1 (ICAM-1) mRNA.
