Poly(vinyl ester) polymers for <i>in vivo </i>nucleic acid delivery

摘要

The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.

主权项

1. A membrane active poly(vinyl ester) random copolymer having the structure represented by: wherein:
N is NH2,Y is (CH2)a, or (CH2)2—O—(CH2)2 wherein a is 1, 2, or 3,R is a hydrophobic group having 2-6 carbon atoms,m and n are independently integers greater than zero (0),the ratio m/n is about 1 to about 4,the poly(vinyl ester) random copolymer is capable of causing red blood cell lysis, andthe polydispersity of the polymer is less than or equal to 1.5.