Polyampholytes for delivering polyions to a cell
View Patent ↗An polyampholyte is utilized in a condensed polynucleotide complex for purposes of nucleic acid delivery to a cell. The complex can be formed with an appropriate amount of positive and/or negative charge such that the resulting complex can be delivered to the extravascular space and may be further delivered to a cell.
1. A process for enhancing delivery of a polyion to a cell, comprising:
a) forming a complex of polyampholyte having groups with pKa's within the physiological range of 4 to 8 and polyion; and,
b) delivering the complex into a cell.
2. The process of claim 1 wherein the polyampholyte contains maleamic acid.
3. The process of claim 2 wherein the polyampholyte is delivered to a cell in vivo.
4. A deliverable complex, comprising: a polyion, and a polyampholyte having groups with pKa's within the physiological range of 4 to 8 wherein the complex is structured to enter a mammalian cell.
5. The complex of claim 4 wherein the polyampholyte contains a bond that is cleavable by a decrease in pH.
6. The complex of claim 5 wherein the polyampholyte contains maleamic acid.
7. The complex of claim 6 wherein the polyampholyte is membrane-disruptive upon cleavage.
8. The complex of claim 7 wherein the polyion comprises a polynucleotide.
9. The complex of claim 8 wherein the polynucleotide comprises an double strand RNA oligonucleotide.
10. The complex of claim 1 wherein the polyampholyte is amphipathic.
11. The complex of claim 1 wherein the polyampholyte contains targeting groups.
12. The complex of claim 11 wherein the targeting group comprises a ligand for a cellular receptor.
13. The complex of claim 12 wherein the cellular receptor consists of an asialoglycoprotein receptor.
14. The complex of claim 1 wherein the polyampholyte contains one or more polyethylene glycol groups.