Amphoteric liposome formulation
View Patent ↗The invention relates to compositions and methods to inhibit gene expression. In particular, the invention provides DNAi oligonucleotides sequestered by amphoteric liposomes for the treatment of cancer.
1. A composition comprising an amphoteric liposome comprising
(i) a DNAi oligonucleotide comprising SEQ ID NOs: 1250 or 1251 or the complements thereof;
(ii) a mixture of lipid components comprising
POPC, DOPE, MoChol, and CHEMS in a molar ratio of POPC/DOPE/MoChol and CHEMS of about 6/24/47/23.
2. The composition of claim 1 , wherein the molar ratio of POPC/DOPE/MoChol/CHEMS is 6/24/47/23.
3. The composition of claim 1 , wherein the amphoteric liposomes comprise a size between about 50 and 500 nm.
4. The composition of claim 1 , wherein the amphoteric liposome comprises a size between about 80 and 200 nm.
5. The composition of claim 1 , wherein the amphoteric liposome has a DNAi oligonucleotide concentration of at least 2 mg/ml at a lipid concentration of about 100 mM or less.
6. The composition of claim 1 , wherein the DNAi oligonucleotide comprises SEQ ID NOs: 1250 or 1251.
7. The composition of claim 1 , wherein the DNAi oligonucleotide comprises SEQ ID NO: 1251.
8. A method comprising
(a) providing the composition of claim 1 , and
(b) introducing the composition into a cell or animal capable of expressing the bcl-2 gene.
9. The method of claim 8 , wherein introducing the composition results in a reduction of proliferation of the cell, or induces cell death.
10. The method of claim 8 , wherein the cell is a cancer cell.
11. The method of claim 8 , wherein the animal is a human.
12. The method of claim 8 , wherein the composition is introduced to the animal by one or more routes of administration selected from topical, pulmonary, intraocular, intranasal, parenteral, and a medical device.
13. The method of claim 8 , wherein the cell is in cell culture.
14. The method of claim 8 , further comprising the step of introducing a chemotherapy agent to the cell or animal.
15. The method of claim 8 , wherein said animal has a cancer which is selected from pancreatic cancer, colon cancer, breast cancer, bladder cancer, lung cancer, leukemia, prostate cancer, lymphoma, ovarian cancer and melanoma.
16. A pharmaceutical composition comprising an amphoteric liposome and a DNAi oligonucleotide comprising SEQ ID NOs:1251 or 1250 wherein the liposome comprises POPC, DOPE, MoChol and CHEMS in the molar ratio of POPC/DOPE/MoChol/CHEMS of 6/24/47/23.