Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
First Claim
1. A nucleic acid-lipid particle for introducing a nucleic acid into a cell, said particle comprising a cationic lipid, a non-cationic lipid, a conjugated lipid that inhibits aggregations of particles, and a nucleic acid, wherein said nucleic acid is encapsulated in the lipid of said particle and is resistant in aqueous solution to degradation with a nuclease, wherein said particle has a charge ratio of cationic lipid to anionic nucleic acid of 1:
- 1 to 8;
1, and wherein;
said cationic lipid is a member selected from the group consisting of N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), and N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), and a mixture of two or more of the above;
said non-cationic lipid is selected from the group consisting of DOPE, POPC, and EPC; and
said conjugated lipid is a PEG-lipid.
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Abstract
Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.
217 Citations
28 Claims
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1. A nucleic acid-lipid particle for introducing a nucleic acid into a cell, said particle comprising a cationic lipid, a non-cationic lipid, a conjugated lipid that inhibits aggregations of particles, and a nucleic acid, wherein said nucleic acid is encapsulated in the lipid of said particle and is resistant in aqueous solution to degradation with a nuclease, wherein said particle has a charge ratio of cationic lipid to anionic nucleic acid of 1:
- 1 to 8;
1, and wherein;said cationic lipid is a member selected from the group consisting of N,N-dioleyl-N,N-dimethylammonium chloride (DODAC), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), and N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA), and a mixture of two or more of the above; said non-cationic lipid is selected from the group consisting of DOPE, POPC, and EPC; and said conjugated lipid is a PEG-lipid. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)
- 1 to 8;
Specification