Cationic lipids for nucleic acid delivery and preparation thereof
AssigneeRamot at Tel-Aviv University Ltd.
InventorsDan PEER, Srinivas RAMISHETTI
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Abstract
The present invention provides cationic lipids and lipid nanoparticle formulations comprising these lipids, alone or in combination with other lipids. These lipid nanoparticles may be formulated with nucleic acids to facilitate their intracellular delivery both in vitro and for therapeutic applications. The present invention also provides methods of chemical synthesis of these lipids, lipid nanoparticle preparation and formulation with nucleic acids.
Claims15
1-24. (canceled)
A cationic lipid, which is represented by the structure of formula (I) or Formula (II) or salts, hydrates, solvates, polymorphs, optical isomers, geometrical isomers, enantiomers, diastereomers, and mixtures thereof, wherein the structures of formula (I) and formula (II) are represented below:
- wherein
- Y is O or NH;
- T is C or S;
- W is S;
- R1 is selected from the group consisting of:
- (a) NR4R5 wherein R4 and R5 are each independently a C1-C4 alkyl;
- or R4 and R5 together with the nitrogen to which they are attached form a 5 or 6 membered heterocyclic or heteroaromatic ring, optionally containing one or more additional heteroatoms selected from the group consisting of O, N and S;
- or NR4R5 represent a guanidine group (—NHC(═NH)NH2);
- (b) the side chain of a natural or unnatural amino acid;
- and
- (c) a 5 or 6 membered heterocyclic or heteroaromatic ring containing one or more heteroatoms selected from the group consisting of O, N and S;
- R2 and R3 are selected from the group consisting of:
- (a) C10-C22 alkyl;
- (b) C10-C22 alkenyl;
- (c) C10-C22 alkynyl;
- (d) C4-C10 alkylene-Z— C4-C22 alkyl;
- and
- (e) C4-C10 alkylene-Z— C4-C22 alkenyl;
- Z is —O—C(═O)—, —C(═O)—O— or —O—;
- n is 0, 1, 2, 3, 4, 5 or 6;
- m is 0 or 1;
- p is 0 or 1;
- and
- z is 0 or 2;
- wherein
- A is
- X′ is O or NH;
- Y′ is O or NH;
- provided that when A is
- X′ and Y′ cannot both be O;
- T is C or S;
- W is a bond, O, NH or S;
- R1 is the side chain of alanine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine;
- R2 and R3 are selected from the group consisting of:
- (a) C10-C22 alkyl;
- (b) C10-C22 alkenyl;
- (c) C10-C22 alkynyl;
- (d) C4-C10 alkylene-Z— C4-C22 alkyl;
- and
- (e) C4-C10 alkylene-Z— C4-C22 alkenyl;
- Z is —O—C(═O)—, —C(═O)—O— or —O—;
- n is 0, 1, 2, 3, 4, 5 or 6;
- m is 0 or 1;
- p is 0 or 1;
- and
- z is 0 or 2
Dependencies are inferred from the claim text.