Compositions and methods for delivering messenger RNA
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.
1. 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 nanoparticle;
provided that the lipid nanoparticle comprises less than 0.5 mole percent phospholipid.
2. The lipid nanoparticle of claim 1 , wherein the PEG-lipid conjugate is selected from the group consisting of a PEG-diacylglycerol (PEG-DAG) conjugate, a PEG-dialkyloxypropyl (PEG-DAA) conjugate, a PEG-ceramide (PEG-Cer) conjugate, and a mixture thereof.
3. The lipid nanoparticle of claim 1 , wherein the PEG-lipid conjugate is a PEG-2000-C-DMA conjugate.
4. The lipid nanoparticle of claim 2 , wherein the PEG-DAA conjugate is selected from the group consisting of a PEG-didecyloxypropyl (C 10 ) conjugate, a PEG-dilauryloxypropyl (C 12 ) conjugate, a PEG-dimyristyloxypropyl (C 14 ) conjugate, a PEG-dipalmityloxypropyl (C 16 ) conjugate, a PEG-distearyloxypropyl (C 18 ) conjugate, and a mixture thereof.
5. The lipid nanoparticle of claim 1 , wherein the lipid nanoparticle has a lipid:nucleic mass ratio of from about 9:1 to about 20:1.
6. The lipid nanoparticle of claim 1 , wherein the mRNA is chemically modified.
7. The lipid nanoparticle of claim 1 , wherein the lipid nanoparticle comprises an electron dense core.
8. The lipid nanoparticle of claim 1 , wherein the lipid nanoparticle comprises an electron dense core and wherein the mRNA is located within the electron dense core.
9. A population of lipid nanoparticles comprising a multiplicity of lipid nanoparticles of claim 1 .
10. A pharmaceutical composition comprising the lipid nanoparticle of claim 1 , and a pharmaceutically acceptable carrier.