CA2079109A1 — Oligonucleotide-transport agent disulfide conjugates

USPTO Abstract

ABSTRACT OF THE DISCLOSURE The invention relates to compositions and methods for enhancing the delivery of an oligonucleotide into a cell. The compositions of the invention comprise oligonucleotide conjugates which consist of an oligonucleotide, conjugated via a molecular linker containing at least one disulfide bond, to an agent (termed herein "transport agent") which facilitates transport across an outer cell membrane, or across the blood-brain barrier. In a preferred aspect, the disulfide linkage is cleaved upon uptake of the composition by the cell. Pharmaceutical compositions comprising an oligonucleotide conjugate of the invention may be used to treat a wide variety of diseases and disorders. Methods for inhibiting the expression of a nucleic acid sequence within a cell, and methods for detecting a nucleic acid sequence within a cell are also provided. In a specific embodiment, an oligonucleotide conjugated to cholesterol via a linker containing a disulfide linkage can be used for therapeutic or diagnostic purposes, by hybridization of the oligonucleotide to a complementary nucleic acid sequence in a procaryotic or eucaryotic cell.