Small molecule conjugates for intracellular delivery of nucleic acids

摘要

The invention provides use of novel compounds for delivery of nucleic acids, and conjugates of these compounds with nucleic acids. Further novel design criteria for chemically stabilized siRNA particular useful when covalently attached to said compounds and co-administered with a delivery polymer to achieve mRNA knock down in vivo are disclosed therein.

主权项

1. A conjugate of formula IV wherein siRNA comprises an antisense strand with the modification pattern 5′-(w)-(Z1)-(Z2)-(Z3)na-3′ and a sense strand with the modification pattern 5′-(Z3)ns-3′, wherein w is independently a 5′-phosphate or 5′-phosphothioate or H, Z1 is independently a 2′-modified nucleotide. Z2 is independently a 2′-deoxy nucleotide or 2′-Fluoro-modified nucleotide, Z3 is independently a 2′-modified nucleotide, na is 8-23 nucleotides and ns is 8-25 nucleotides.