ENGINEERING SYNTHETIC BRAIN PENETRATING GENE VECTORS
First Claim
1. A nanoparticle formulation for delivery of nucleic acid to tissue including brain, comprisingnucleic acids;
- a first hydrophilic cationic polymer; and
a second hydrophilic, neutrally charged linear or branched polymer selected from the group consisting of polyethylene glycol, polyethylene oxide, and copolymers thereof,wherein between 90% and 75% of the cationic polymer is conjugated to the hydrophilic polymer or wherein at least 50% of the cationic polymer is conjugated to a branched hydrophilic polymer, wherein the nucleic acid is encapsulated within the nanoparticle or associated with the surface of the nanoparticle and wherein the nanoparticle is coated with the hydrophilic polymer at a density that imparts a near neutral charge and enhances the diffusivity through the tissue.
2 Assignments
0 Petitions
Accused Products
Abstract
A synthetic gene delivery platform with a dense surface coating of hydrophilic and neutrally charged PEG, capable of rapid diffusion and widespread distribution in brain tissue, and highly effective gene delivery to target cells therein has been developed. Nanoparticles including nucleic acids, are formed of a blend of biocompatible hydrophilic cationic polymers and they hydrophilic cationic polymer conjugated to hydrophilic neutrally charged polymers such as polyethylene glycol. The nanoparticles are coated with polyethylene glycol at a density that imparts a near neutral charge and optimizes rapid diffusion through the brain parenchyma. Methods of treating a disease or disorder of the brain including administering a therapeutically effective amount of nanoparticles densely coated with polyethylene glycol are also provided.
-
Citations
26 Claims
-
1. A nanoparticle formulation for delivery of nucleic acid to tissue including brain, comprising
nucleic acids; -
a first hydrophilic cationic polymer; and a second hydrophilic, neutrally charged linear or branched polymer selected from the group consisting of polyethylene glycol, polyethylene oxide, and copolymers thereof, wherein between 90% and 75% of the cationic polymer is conjugated to the hydrophilic polymer or wherein at least 50% of the cationic polymer is conjugated to a branched hydrophilic polymer, wherein the nucleic acid is encapsulated within the nanoparticle or associated with the surface of the nanoparticle and wherein the nanoparticle is coated with the hydrophilic polymer at a density that imparts a near neutral charge and enhances the diffusivity through the tissue. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
-
Specification