MUCUS PENETRATING GENE CARRIERS

摘要

Nanoparticles gene carriers, particularly nanoparticle gene carriers which exhibit increased rates of diffusion through cystic fibrosis (CF) mucus, as well as methods of making and using thereof, are described herein. The nanoparticle gene carriers are formed from a nucleic acid complexed to one or more biocompatible, polycationic polymers. The nanoparticle gene carriers also contain one or more mucus resistant polymers. In a particularly preferred embodiment, the nanoparticle gene carrier is a nanoparticle formed from one or more nucleic acids, PEI, and a mucus-resistant/diffusive graft copolymer composed of a PEI backbone functionalized by one or more PEG side chains. The nanoparticle gene carriers can efficiently diffuse through CF mucus, and can effectively serve as a vehicle to administer one or more nuleic acids to a patient suffering from CF.

主权项

1. A composition for delivery of nucleic acid comprising nanoparticles comprising
a) a complex formed by the ionic association of one or more nucleic acids and one or more polycationic polymers, and b) one or more mucus-resistant/diffusive graft co-polymers non-covalently associated to the complex, wherein the nanoparticles have an average diameter of between 5 and 500 nm, wherein the one or more mucus-resistant/diffusive graft co-polymers comprise a polycationic polymer backbone having multiple mucus-resistant/diffusive polymer side chains covalently attached thereto, and wherein the ratio of mucus-resistant/diffusive polymer side chains to the polycationic backbone is between 15:1 and 60:1, or wherein the one or more polycationic polymers and one or more mucus-resistant/diffusive graft co-polymers are present in a molar ratio of between 1:5 and 5:1.