Compositions and methods for delivering messenger rna
AssigneeArbutus Biopharma Corporation
InventorsMichael J. ABRAMS, James HEYES, Adam JUDGE, Kieu Mong LAM, Lorne Ralph PALMER, Stephen P. REID, Edward D. YAWORSKI
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Abstract
The present invention provides compositions comprising nucleic acid molecules, such as mRNA molecules, encapsulated within lipid particles. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease.
Claims31
A lipid nanoparticle comprising:
- (a) a cationic lipid;
- (b) a non-cationic lipid;
- (c) a corticosteroid and;
- (d) a nucleic acid, wherein the nucleic acid and the corticosteroid are encapsulated within the lipid nanoparticle.
A population of lipid nanoparticles, comprising at least one population of lipid nanoparticles selected from:
- (a) a first population of lipid nanoparticles that each comprise a cationic lipid, a non-cationic lipid, and a corticosteroid;
- and
- (b) a second population of lipid nanoparticles that each comprise a cationic lipid, a non-cationic lipid, and a nucleic acid,
- wherein the first population of lipid nanoparticles does not comprise a nucleic acid, and wherein the second population of lipid nanoparticles does not comprise a corticosteroid.
A lipid nanoparticle formulation comprising a multiplicity of lipid nanoparticles, wherein each lipid nanoparticle comprises:
- (a) a cationic lipid;
- (b) a non-cationic lipid;
- and
- (c) mRNA encapsulated within the lipid particle,
- wherein the lipid nanoparticle formulation has an IFIT response that is no more than 30 fold greater than a reference IFIT response of phosphate buffered saline.
A method of making a lipid nanoparticle, comprising combining:
- (a) a cationic lipid;
- (b) a non-cationic lipid;
- and
- (c) purified mRNA so as to form a lipid nanoparticle, wherein the mRNA is encapsulated within the lipid nanoparticle, and wherein the lipid nanoparticle has an IFIT response that is no more than 30 fold greater than a reference IFIT response of phosphate buffered saline.
A method of making a lipid nanoparticle formulation comprising a multiplicity of lipid nanoparticles, the method comprising the step of combining:
- (a) a cationic lipid;
- (b) a non-cationic lipid;
- and
- (c) purified mRNA so as to form a lipid nanoparticle formulation comprising a multiplicity of lipid nanoparticles, wherein the mRNA is encapsulated within the lipid particles in the lipid nanoparticle formulation, and wherein the lipid nanoparticle formulation has an IFIT response that is no more than 30 fold greater than a reference IFIT response of phosphate buffered saline.
A lipid nanoparticle formulation comprising a multiplicity of lipid nanoparticles made by a process comprising the steps of combining:
- (a) a cationic lipid;
- (b) a non-cationic lipid;
- and
- (c) purified mRNA so as to form a lipid nanoparticle formulation comprising a multiplicity of lipid nanoparticles, wherein the mRNA is encapsulated within the lipid particles in the lipid nanoparticle formulation, and wherein the lipid nanoparticle formulation has an IFIT response that is no more than 30 fold greater than a reference IFIT response of phosphate buffered saline.
A lipid nanoparticle comprising:
- (a) a cationic lipid;
- (b) a PEG-lipid conjugate present in an amount of at least 3 mole percent;
- and
- (c) mRNA encapsulated within the lipid particle;
- provided that the lipid particle comprises less than 0.5 mole percent phospholipid.
A population of lipid nanoparticles wherein each lipid nanoparticle in the population comprises:
- (a) a cationic lipid;
- (b) a PEG-lipid conjugate present in an amount of at least 3 mole percent;
- and
- (c) mRNA encapsulated within the lipid nanoparticle;
- provided that the lipid nanoparticle comprises less than 0.5 mole percent phospholipid.
Dependencies are inferred from the claim text.