Delivery system for nucleic acids
AssigneesThe Scripps Research Institute, The Board of Trustees of the Leland Stanford Jr. University
InventorsDavid Cheresh, John Hood, Mark Bednarski
Life of this patent
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Abstract
αvβ3 Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic αvβ3 integrin antagonist.
Claims14
An αvβ3 integrin receptor targeting liposome comprising
- a cationic lipid;
- a neutral lipid;
- a targeting lipid having a targeting domain and a hydrophobic domain bound to the targeting domain;
- and
- a nucleic acid complexed with the cationic lipid;
- the cationic lipid being present in an amount in the range of about 1 to about 50 mole percent, and said targeting lipid being present in an amount in the range of about 1 to about 20 mole percent, the mole percent values being based on total moles of lipid in the liposome, and the targeting domain including a non-peptidic αvβ3 integrin antagonist represented by formula (II):
- wherein in formula (II), R4 and R5 are each hydrogen, or together form a covalent bond;
- Y is —C(O)— or —CH2—;
- Z2 is —C(O)—R6;
- —C(O)OR6, or SO2R6;
- R6 is phenyl, substituted-phenyl, pyridyl, benzyl, substituted-benzyl;
- C1-C4 haloalkyl, C2-C30 alkyl, C2-C30 alkenyl, C2-C30 alkynyl, or cholesteryl;
- and Het is 2-pyridyl or 2-imidazolyl.
A method for inhibiting angiogenesis which comprises administering to a patient in need of angiogenesis inhibition a therapeutically effective amount of an αvβ3 integrin receptor targeting liposome, the liposome comprising
- a cationic lipid,
- a neutral lipid,
- a targeting lipid having a targeting domain and a hydrophobic domain bound to the targeting domain, and
- a nucleic acid complexed with the cationic lipid, the nucleic acid being capable of expressing an angiogenesis inhibiting protein or peptide;
- the cationic lipid being present in an amount in the range of about 1 to about 50 mole percent, and said targeting lipid being present in an amount in the range of about 1 to about 20 mole percent, the mole percent values being based on total moles of lipid in the liposome, and the targeting domain including a non-peptidic αvβ3 integrin receptor antagonist.
A method for inhibiting tumor growth which comprises administering to a patient in need of tumor growth inhibition a therapeutically effective amount of an αvβ3 integrin receptor targeting liposome, the liposome comprising
- a cationic lipid,
- a neutral lipid,
- a targeting lipid having a targeting domain and a hydrophobic domain bound to the targeting domain, and
- a nucleic acid complexed with the cationic lipid, the nucleic acid being capable of expressing an angiogenesis inhibiting protein or peptide;
- the cationic lipid being present in an amount in the range of about 1 to about 50 mole percent, and said targeting lipid being present in an amount in the range of about 1 to about 20 mole percent, the mole percent values being based on total moles of lipid in the liposome, and the targeting domain including a non-peptidic αvβ3 integrin receptor antagonist.
A method for inducing apoptosis in vascular endothelial cells which comprises contacting vascular endothelial cells with an apoptosis inducing effective amount of an αvβ3 integrin receptor targeting liposome, the liposome comprising
- a cationic lipid,
- a neutral lipid,
- a targeting lipid having a targeting domain and a hydrophobic domain bound to the targeting domain, and
- a nucleic acid complexed with the cationic lipid, the nucleic acid being capable of expressing an apoptosis inducing protein or peptide;
- the cationic lipid being present in an amount in the range of about 1 to about 50 mole percent, and said targeting lipid being present in an amount in the range of about 1 to about 20 mole percent, the mole percent values being based on total moles of lipid in the liposome, and the targeting domain including a non-peptidic αvβ3 integrin antagonist.
Dependencies are inferred from the claim text.