Compositions and methods for drug delivery using pH sensitive molecules
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 delivering a nucleic acid to a cell comprising:
a) condensing a nucleic acid with a polyampholyte to form a complex;
b) crosslinking the polyampholyte; and,
c) contacting the cell with the crosslinked complex.
2. The process of claim 1 wherein the nucleic acid consists essentially of RNA.
3. The process of claim 1 wherein the nucleic acid consists of an oligonucleotide.
4. The process of claim 1 wherein the crosslinked complex is less in 100 nm in size.
5. The process of claim 1 wherein the nucleic acid consists of DNA.
6. The process of claim 5 wherein the DNA contains an expressible sequence.
7. The process of claim 1 wherein the polyampholyte consists of a labile polyampholyte.
8. The process of claim 7 wherein the polyampholyte consists of a pH labile polyampholyte.
9. The process of claim 8 wherein the polyampholyte contains at least one pH labile bond in which the half-life of the pH labile bond is less than 45 minutes at pH 5.
10. The process of claim 8 wherein the polyampholyte contains at least one pH labile bond in which the half-life of the pH labile bond is less than 15 minutes at pH 5.
11. A particle for delivering a nucleic acid to a cell formed by the process comprising:
a) condensing a nucleic acid with a polycation to form a complex;
b) adding a polyanion to the complex to form a tertiary complex; and
c) crosslinking the polyanion to the polycation to form a particle.
12. The particle of claim 11 wherein the polycation contains a labile bond.
13. The particle of claim 11 wherein the polyanion contains a labile bond.
14. The particle of claim 11 wherein crosslinking the polyanion to the polycation forms a multivalent block polyampholyte.
15. The particle of claim 11 wherein the polyanion is crosslinked to the polycation via a labile bond.
16. The particle of claim 11 wherein crosslinking the polyanion to the polycation comprises adding a crosslinker to the tertiary complex.
17. The particle of claim 16 wherein the crosslinker contains a labile bond.
18. The particle of claim 11 wherein the nucleic acid consists essentially of RNA.
19. The particle of claim 11 wherein the nucleic acid consists of an oligonucleotide.
20. The particle of claim 11 wherein the nucleic acid consists of DNA.
21. The particle of claim 20 wherein the DNA contains an expressible sequence.
22. A process for delivering a nucleic acid to a cell comprising:
a) condensing a nucleic acid with a polycation to form a complex,
b) adding a polyanion to the complex to form a tertiary complex,
c) crosslinking the polyanion to the polycation to form a particle; and,
d) contacting the cell with the particle.
23. The process of claim 22 wherein the polycation contains a labile bond.
24. The process of claim 22 wherein the polyanion contains a labile bond.
25. The process of claim 22 wherein crosslinking the polyanion to the polycation forms a multivalent block polyampholyte.
26. The process of claim 22 wherein the polyanion is crosslinked to the polycation via a labile bond.
27. The process of claim 22 wherein crosslinking the polyanion to the polycation comprises adding a crosslinker to the tertiary complex.
28. The process of claim 27 wherein the crosslinker contains a labile bond.
29. The process of claim 22 wherein the nucleic acid consists essentially of RNA.
30. The process of claim 22 wherein the nucleic acid consists of an oligonucleotide.
31. The process of claim 22 wherein the nucleic acid consists of DNA.
32. The process of claim 31 wherein the DNA contains an expressible sequence.