Cationic phospholipids for transfection
AssigneeNorthwestern University
InventorsGary W. Ashley, Robert C. MacDonald, Miho Shida
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Abstract
A novel class of cationic phospholipids and novel method for their synthesis are disclosed. The class of phospholipids comprises phosphotriester derivatives of phosphoglycerides and sphingolipids. It has been unexpectedly found that liposomes comprising one or more of these cationic phospholipids are effective in the lipofection of nucleic acids. These novel phospholipids are particularly attractive because of they are not only effective in lipofection, but are extremely cheap and easy to male.
Claims10
A cationic phospholipid having the structure:
- wherein
- R1 and R2 independently are H or C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chains optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety,
- R3 is hydrogen or methyl,
- R4 is a C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chain optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety, or R4 is a C1 to about C6 straight or branched chain ester, aldehyde, ketone, ether, haloalkyl, azidoalkyl, or tetraalkylanmronium,
- n is 0, 1, 2, or 3,
- s is 0 or 1, and
- t is 0 or 1,
- provided that R1 and R2 are not both H and that when R1 is H, s is 0, and that when R2 is H, t is 0.
A liposome-nucleic acid aggregate comprising one or more nucleic acids and one or more liposomes comprising one or more cationic lipids having the structure:
- wherein
- R1 and R2 independently are H or C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chains optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety,
- R3 is hydrogen or methyl,
- R4 is a C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chain optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety, or R4 is a C1 to about C6 straight or branched chain ester, aldehyde, ketone, ether, haloalkyl, azidoalkyl, or tetraalkylammonium,
- n is 0, 1, 2, or 3,
- s is 0 or 1, and
- t is 0 or 1,
- provided that R1 and R2 are not both H and that when R1 is H, s is 0, and that when R2 is H, t is 0.
A liposome-drug aggregate comprising one or more liposomes comprising one or more cationic lipids having the structure:
- wherein
- R1 and R2 independently are H or C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chains optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety,
- R3 is hydrogen or methyl,
- R4 is a C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chain optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety, or R4 is a C1 to about C6 straight or branched chain ester, aldehyde, ketone, ether, haloalkyl, azidoalkyl, or tetraalkylanmronium,
- n is 0, 1, 2, or 3,
- s is 0 or 1, and
- t is 0 or 1,
- provided that R1 and R2 are not both H and that when R1 is H, s is 0, and that when R2 is H, t is 0,
- and one or more associated drugs.
A liposome comprising one or more cationic lipids having the structure:
- wherein
- R4 is a C1 to about C24 straight or branched alkyl, alkenyl, or alkynyl chain optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety, or R4 is a C1 to about C6 straight or branched chain ester, aldehyde, ketone, ether, haloalkyl, azidoalkyl, or tetraalkylammonium,
- R5 is H or a C1 to about C24 straight or branched alkyl, alkenyl, or a alkynyl chains optionally substituted with a dansyl, NBD, DPH, carbocyclic aromatic, or heterocyclic moiety.
Dependencies are inferred from the claim text.