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US 8,895,717 B2Granted
Delivery of siRNA by neutral lipid compositions
AssigneeBoard of Regents, The University of Texas System
InventorsAnil K. Sood, Gabriel Lopez-Berestein, Charles N. Landen, Arturo Chavez-Reyes
Life of this patent
Estimating the term…
Abstract
The present invention relates to the fields of molecular biology and drug delivery. In certain embodiments, the present invention provides methods for the delivery of a siNA (e.g., a siRNA) to a cell via a neutral (non-charged) liposome. These methods may be used to treat a disease, such as cancer.
Claims12
A pharmaceutical composition comprising:
- (a) a short inhibitory ribonucleic acid (siRNA) component comprising one or more siRNA, wherein the siRNA has a backbone moiety that is negatively charged;
- and
- (b) a lipid component comprising a phospholipid component consisting of one or more neutral phospholipids selected from the group consisting of a phosphatidylcholine or a phosphatidylethanolamine phospholipid, wherein the phospholipid is not a lysophosphatidylcholine or lysophosphatidylethanolamine and further wherein the lipid component has a neutral charge;
- wherein the lipid component forms a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA, the siRNA is a double stranded nucleic acid of 18 to 100 nucleobases, and the liposome encapsulated siRNA is comprised in a pharmaceutically acceptable carrier, wherein the phospholipid component consists of DOPC.
1 more element
A pharmaceutical composition comprising:
- (a) a short inhibitory ribonucleic acid (siRNA) component comprising one or more siRNA, wherein the siRNA has a backbone moiety that is negatively charged;
- and
- (b) a lipid component comprising a phospholipid component consisting of one or more neutral phospholipids selected from the group consisting of a phosphatidylcholine or a phosphatidylethanolamine phospholipid, wherein the phospholipid is not a lysophosphatidylcholine or lysophosphatidylethanolamine and further wherein the lipid component has a neutral charge;
- wherein the lipid component forms a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA, the siRNA is a double stranded nucleic acid of 18 to 100 nucleobases, and the liposome encapsulated siRNA is comprised in a pharmaceutically acceptable carrier, wherein the phospholipid component consists of two or more types of neutral phospholipids.
1 more element
A pharmaceutical composition comprising:
- (a) a short inhibitory ribonucleic acid (siRNA) component comprising one or more siRNA, wherein the siRNA has a backbone moiety that is negatively charged;
- and
- (b) a lipid component comprising a phospholipid component consisting of one or more neutral phospholipids selected from the group consisting of a phosphatidylcholine or a phosphatidylethanolamine phospholipid, wherein the phospholipid is not a lysophosphatidylcholine or lysophosphatidylethanolamine and further wherein the lipid component has a neutral charge;
- wherein the lipid component forms a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA, the siRNA is a double stranded nucleic acid of 18 to 100 nucleobases, and the liposome encapsulated siRNA is comprised in a pharmaceutically acceptable carrier, wherein the siRNA inhibits the translation of a gene that promotes growth of a hyperplastic or cancerous mammalian cell and wherein the gene is EphA2.
1 more element
A pharmaceutical composition comprising:
- (a) a short inhibitory ribonucleic acid (siRNA) component comprising one or more siRNA, wherein the siRNA has a backbone moiety that is negatively charged;
- and
- (b) a lipid component comprising a phospholipid component consisting of one or more neutral phospholipids selected from the group consisting of a phosphatidylcholine or a phosphatidylethanolamine phospholipid, wherein the phospholipid is not a lysophosphatidylcholine or lysophosphatidylethanolamine and further wherein the lipid component has a neutral charge;
- wherein the lipid component forms a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA, the siRNA is a double stranded nucleic acid of 18 to 100 nucleobases, and the liposome encapsulated siRNA is comprised in a pharmaceutically acceptable carrier wherein the siRNA inhibits the translation of a gene that promotes growth of a hyperplastic or cancerous mammalian cell and wherein the gene is β2 adrenergic receptor (β2AR).
1 more element
A pharmaceutical composition comprising:
- (a) a short inhibitory ribonucleic acid (siRNA) component comprising one or more siRNA, wherein the siRNA has a backbone moiety that is negatively charged;
- and
- (b) a lipid component comprising a phospholipid component consisting of one or more neutral phospholipids selected from the group consisting of a phosphatidylcholine or a phosphatidylethanolamine phospholipid, wherein the phospholipid is not a lysophosphatidylcholine or lysophosphatidylethanolamine and further wherein the lipid component has a neutral charge;
- wherein the lipid component forms a liposome that encapsulate the siRNA such that greater than 90% of the liposomes encapsulate siRNA, the siRNA is a double stranded nucleic acid of 18 to 100 nucleobases, and the liposome encapsulated siRNA is comprised in a pharmaceutically acceptable carrier, wherein the siRNA inhibits the translation of a gene that promotes growth of a hyperplastic or cancerous mammalian cell and wherein the gene is focal adhesion kinase (FAK).
1 more element
Dependencies are inferred from the claim text.