MRNA THERAPEUTIC COMPOSITIONS AND USE TO TREAT DISEASES AND DISORDERS
Disclosed are compositions and methods for producing therapeutic fusion proteins in vivo. The compositions and methods disclosed herein are capable of ameliorating diseases by providing therapeutic protein delivery.
1 . A composition comprising (a) at least one mRNA molecule, at least a portion of which encodes a therapeutic polypeptide fused to a polypeptide capable of binding to an Fc receptor; and (b) a transfer vehicle.
2 . The composition of claim 1 , wherein the polypeptide capable of binding to an Fc receptor is an FcRn binding peptide.
3 . The composition of claim 1 , wherein the polypeptide capable of binding to an Fc receptor is an immunoglobulin Fc domain.
4 . The composition of claim 3 , wherein the immunoglobulin Fc domain is from IgG.
5 . The composition of claim 1 , wherein the Fc receptor is the neonatal Fc receptor, FcRn.
6 . The composition of claim 1 , wherein the mRNA molecule comprises at least one modification which confers stability on the mRNA molecule.
7 . The composition of claim 1 , wherein the mRNA molecule comprises a 5′ untranslated region.
8 - 16 . (canceled)
17 . The composition of claim 1 , where in the mRNA encodes a protein which is abnormal or deficient in an individual.
18 - 23 . (canceled)
24 . The composition of claim 1 , formulated for pulmonary administration.
25 . The composition of claim 1 , wherein the delivery vehicle is polyethyleneimine (PEI).
26 . (canceled)
27 . The composition of claim 1 , wherein the delivery vehicle is a lipid nanoparticle.
28 . The composition of claim 27 , wherein the lipid nanoparticle comprises one or more cationic lipids.
29 . (canceled)
30 . The composition of claim 27 , wherein the lipid nanoparticle comprises one or more non-cationic lipids.
31 . The composition of claim 27 , wherein the lipid nanoparticle comprises one or more PEG-modified lipids.
32 . The composition of claim 27 , wherein the lipid nanoparticle comprises a cholesterol.
33 - 37 . (canceled)
38 . The composition of claim 1 , wherein said composition is lyophilized.
39 . (canceled)
40 . A method of inducing expression of a functional polypeptide in a subject, comprising administering the composition of claim 1 .
41 - 42 . (canceled)
43 . The method of claim 40 , wherein the composition is administered by nebulization, aerosolization, or instillation.
44 . A composition comprising (a) at least one mRNA molecule at least a portion of which encodes a therapeutic protein fused to a polypeptide capable of binding to an Fc receptor; and (b) a transfer vehicle comprising a lipid nanoparticle or a lipidoid nanoparticle, wherein the polypeptide is chosen from proteins listed in table S1, table S2, and table S3, mammalian homologs thereof, and homologs from animals of veterinary or industrial interest.