Compositions for Targeted Delivery of siRNA

摘要

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted delivery polymers. Delivery polymers provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery polymers.

主权项

1. A composition for delivering an RNA interference polynucleotide to a cell in vivo comprising: wherein, P is a membrane active polyamine, L2 is an physiologically labile linkage, M1 comprises a galactose or galactose derivative having affinity for the asialoglycoprotein receptor, M2 comprises a steric stabilizer, y is an integer greater than 1 z is an integer greater than or equal to zero the value y+z is greater than 50% of the number of amines on P, N is an RNA interference polynucleotide, and A comprises a hydrophobic group having at least 20 carbon atoms.