Charge Reversal of Polyion Complexes
An ionic polymer is utilized in “recharging” (another layer having a different charge) a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The resulting recharged complex can be formed with an appropriate amount of positive or negative charge such that the resulting complex has the desired net charge.
1 A process for delivering a nucleic acid to a cell in vivo, comprising:
a) forming a composition consisting of a nucleic acid associated via a non-covalent ionic interaction with a polycation in a solution wherein the composition has a net charge less negative than the nucleic acid;
b) ionically associating a polyanion with the composition of step a) in sufficient amount to form a complex having a net negative charge;
c) inserting the complex into a mammal;
d) delivering the complex to the cell.
2 . The process of claim 1 wherein the polycation is selected from the group consisting of polylysine and polyethylenimine.
3 . The process of claim 1 wherein the polyanion comprises a molecule selected from the group consisting of succinylated PLL, succinylated PEI, polyglutamic acid, polyaspartic acid, polyacrylic acid, polymethacrylic acid, dextran sulfate, heparin, hyaluronic acid, DNA, RNA, and negatively charged proteins.
4 . The process of claim 1 wherein the polyanion comprises a block co-polymer.
5 . The process of claim 1 wherein the polyanion comprises a molecule selected from the group consisting of pegylated derivatives, pegylated derivatives carrying specific ligands, block copolymers, graft copolymers and hydrophilic polymers.