Lipid nanoparticles compositions
AssigneeIntellia Thrapeutics, Inc.
InventorsArchana Swami, Vishal Rakshe, Aaron Prodeus, Micah Maetani, Rubina Giare Parmar
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Abstract
The disclosure provides lipid nanoparticle (LNP) compositions of ionizable lipids, helper lipids, neutral lipids, and PEG lipids useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The LNP compositions disclosed herein are useful in methods of gene editing and methods of delivering a biologically active agent and methods of modifying or cleaving DNA.
Claims191
A lipid composition comprising:
- a biologically active agent;
- and
- a lipid component, wherein the lipid component comprises:
- a) an ionizable lipid in an amount from about 25-50 mol % of the lipid component;
- b) a neutral lipid in an amount from about 7-25 mol % of the lipid component;
- c) a helper lipid in an amount from about 39-65 mol % of the lipid component;
- and
- d) a PEG lipid in an amount from about 0.5-1.8 mol % of the lipid component;
- wherein the ionizable lipid is a compound of Formula (I)
- wherein
- X1 is C6-7 alkylene;
- X2 is
- or absent, provided that if X2 is
- R2 is not alkoxy;
- Z1 is C2-3 alkylene;
- Z2 is selected from —OH, —NHC(═O)OCH3, and —NHS(═O)2CH3;
- R1 is C7-9 unbranched alkyl or C7-11 unbranched alkynyl;
- and
- each R2 is independently C8 alkyl or C8 alkoxy;
- or a salt thereof.
A lipid composition comprising:
- a biologically active agent;
- and
- a lipid component, wherein the lipid component comprises:
- a) an ionizable lipid in an amount from about 25-50 mol % of the lipid component;
- b) a neutral lipid in an amount from about 7-25 mol % of the lipid component;
- c) a helper lipid in an amount from about 39-65 mol % of the lipid component;
- and
- d) a PEG lipid in an amount from about 0.5-1.8 mol % of the lipid component;
- wherein the ionizable lipid is a compound of Formula (I)
- wherein
- X1 is C6-7 alkylene;
- X2 is
- or absent, provided that if X2 is
- R2 is not alkoxy;
- Z1 is C2-3 alkylene;
- Z2 is selected from —OH, —NHC(═O)OCH3, and —NHS(═O)2CH3;
- R1 is C7-9 unbranched alkyl;
- and
- each R2 is independently C8 alkyl or C8 alkoxy;
- or a salt thereof.
A lipid composition comprising:
- a biologically active agent;
- and
- a lipid component, wherein the lipid component comprises:
- a) an ionizable lipid in an amount from about 25-50 mol % of the lipid component;
- b) a neutral lipid in an amount from about 7-25 mol % of the lipid component;
- c) a helper lipid in an amount from about 39-65 mol % of the lipid component;
- and
- d) a PEG lipid in an amount from about 0.5-1.8 mol % of the lipid component;
- wherein the ionizable lipid is
- or a salt thereof.
The lipid composition of any one of the preceding claims, wherein the ionizable lipid is
- or a salt thereof.
The lipid composition of any one of the preceding claims, wherein the ionizable lipid is
- or a salt thereof.
The lipid composition of any one of the preceding claims, wherein the neutral lipid is an uncharged lipid or a zwitterionic lipid.
The lipid composition of any one of the preceding claims, wherein the neutral lipid is DSPC or DPME.
The lipid composition of any one of the preceding claims, wherein the neutral lipid is DSPC.
The lipid composition of any one of the preceding claims, wherein the helper lipid is selected from cholesterol, 5-heptadecylresorcinol, and cholesterol hemisuccinate.
The lipid composition of any one of the preceding claims, wherein the helper lipid is cholesterol.
The lipid composition of any one of the preceding claims, wherein the PEG lipid comprises dimyristoylglycerol (DMG).
The lipid composition of any one of the preceding claims, wherein the PEG lipid comprises PEG-2k.
The lipid composition of any one of the preceding claims, wherein the PEG lipid is a PEG-DMG.
The lipid composition of any one of the preceding claims, wherein the PEG lipid is PEG-2k DMG.
The lipid composition of any one of the preceding claims, wherein the ionizable lipid is
- the neutral lipid is DSPC;
- the helper lipid is cholesterol;
- and the PEG lipid is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000.
The lipid composition of any one of the preceding claims, wherein the amount of the ionizable lipid is from about 30-45 mol % of the lipid component.
The lipid composition of any one of the preceding claims, wherein the amount of the neutral lipid is from about 10-20 mol % of the lipid component.
The lipid composition of any one of the preceding claims, wherein the amount of the helper lipid is from about 50-60 mol % of the lipid component.
The lipid composition of any one of the preceding claims, wherein the amount of the PEG lipid is from about 0.9-1.6 mol % of the lipid component.
The lipid composition of any one of the preceding claims, wherein each mol % varies by less than 5%.
The lipid composition of any one of the preceding claims, wherein each mol % varies by less than 1%.
The lipid composition of any one of the preceding claims, wherein each mol % varies by less than 0.5%.
The lipid composition of any one of the preceding claims, wherein each mol % is based on the relative nominal concentrations of the ionizable lipid, the neutral lipid, the helper lipid, and the PEG lipid.
The lipid composition of any one of the preceding claims, wherein each mol % is based on the relative actual concentrations of the ionizable lipid, the neutral lipid, the helper lipid, and the PEG lipid.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have a Z-average diameter of less than about 100 nm.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have a Z-average diameter of less than about 95 nm.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have a Z-average diameter of less than about 90 nm.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have number-average diameter of greater than about 45 nm.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have number-average diameter of greater than about 50 nm.
The lipid composition of any one of the preceding claims, wherein the lipid composition is in the form of LNPs;
- and the LNPs have a polydispersity index of about 0.005 to about 0.75.
The lipid composition of any one of the preceding claims, wherein the LNP composition is in the form of LNPs;
- and the LNPs have a polydispersity index of about 0.005 to about 0.1.
The lipid composition of any one of the preceding claims, wherein the N/P ratio of the lipid composition is from about 5 to about 7.
The lipid composition of any one of the preceding claims, wherein the N/P ratio of the lipid composition is about 6.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises a non-nucleic acid component.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises or encodes a therapeutically active protein.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises or encodes a genome-editing tool.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises or encodes one or more nucleases capable of making single or double strand break in a DNA or an RNA.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises a nucleic acid component.
The lipid composition of any one of the preceding claims, wherein the biologically active agent comprises an RNA.
The lipid composition of any one of the preceding claims, wherein the lipid composition is an LNP composition.
A method of gene editing, comprising contacting a cell with a lipid composition of any one of the preceding claims.
The method of claim 166, wherein the population of cells is a population of human cells.
Dependencies are inferred from the claim text.