Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.
1. An mRNA encoding a polypeptide of interest comprising SEQ ID NO: 5562, wherein said mRNA comprises a coding region having at least 80% identity to SEQ ID NO: 14594.
2. The mRNA of claim 1 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.
3. The mRNA of claim 2 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.
4. The mRNA of claim 2 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.
5. The mRNA of claim 2 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.
6. The mRNA of claim 2 , wherein the mRNA comprises at least two stop codons.
7. A pharmaceutical composition comprising the mRNA of claim 1 and a pharmaceutically acceptable excipient.
8. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable excipient is selected from a solvent, aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex, peptide, protein, cell, hyaluronidase, and mixtures thereof.
9. The pharmaceutical composition of claim 8 , where the pharmaceutical composition comprises a lipid and wherein said lipid is selected from DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA and PEGylated lipids and mixtures thereof.
10. A method of producing a polypeptide of interest in a mammalian cell, tissue or organism comprising contacting said cell, tissue or organism with the mRNA of claim 1 .
11. The method of claim 10 , wherein the mRNA is formulated.
12. The method of claim 11 , wherein the formulation comprises a lipid which is selected from the group consisting of DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA, PEGylated lipids and mixtures or combinations thereof.
13. The method of claim 10 , wherein the contacting is a route of administration selected from the group consisting of intramuscular, intradermal, intravenous and subcutaneous.
14. The method of claim 13 , wherein the route of administration is intramuscular.
15. The method of claim 10 , wherein the mRNA comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.
16. The method of claim 15 , wherein the 5′ untranslated region is heterologous to the coding region of the mRNA.
17. The method of claim 15 , wherein the 3′ untranslated region is heterologous to the coding region of the mRNA.
18. The method of claim 15 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the mRNA.
19. The method of claim 15 , wherein the mRNA comprises at least two stop codons.