METHODS AND COMPOSITIONS FOR ENHANCING DELIVERY OF DOUBLE-STRANDED RNA OR A DOUBLE-STRANDED HYBRID NUCLEIC ACID TO REGULATE GENE EXPRESSION IN MAMMALIAN CELLS.

摘要

Cholesterol moieties are linked to specific ends of double-stranded RNA, preferablya small, interfering (si)RNA or to a dsHybrid. The dsHybrid has one strand comprisedof DNA and one strand comprised of RNA. Preferably the sense strand is the DNA strandand the antisense strand is the RNA strand of the dsHybrid. The present inventionis based upon the discovery that a cholesterol moiety, if linked to a specificend or ends of the sense or antisense strands of a siRNA, can enhance the deliveryand silencing efficiency of the siRNA directed against its target message, incomparison with a corresponding, non-conjugated siRNA. Conjugated siRNAsand dsHybrids of the invention are optionally formulated with, or coordinatelyadministered with, a secondary delivery-enhancing agent, such as a delivery-enhancingpeptide, to enhance intracellular delivery and uptake of the conjugated siRNAsor dsHybrid.