Patent ID: 8313772

Claim:
A conjugate delivery system for delivering an RNA interference polynucleotide to a liver cell in vivo comprising: wherein, P is a membrane active polyamine L 2 is a disubstituted maleamate linkage, M 1 is a charge neutral masking agent containing a galactose derivative having affinity for the asialoglycoprotein receptor, M 2 is a charge neutral masking agent containing a polyethylene glycol, y and z are integers greater than 1 wherein the value of y and z together is greater than 50% of amines on P, N is an RNA interference polynucleotide, A is a hydrophobic group having at least 20 carbon atoms, positive charge of P is neutralized and membrane activity of P is reversibly inhibited by modification of greater than 50% of P amines by attachment of M 1 and M 2 through the physiologically pH-labile linkages L 2 , and cleavage of L 2 in response to a decrease in pH restores amines and membrane activity_of P.