Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.
1. A composition comprising at least one mRNA, said mRNA comprising
a first region of linked nucleosides encoding SEQ ID NOs 41713, wherein said first region of linked nucleosides comprise a coding region having at least 80% identity to SEQ ID NO: 249789.
2. The composition of claim 1 , wherein the at least one mRNA comprises a poly-A tail.
3. The composition of claim 2 , wherein the at least one mRNA comprises a 5′ cap structure.
4. The composition of claim 2 , wherein the at least one mRNA is purified.
5. The composition of claim 1 , comprising a pharmaceutically acceptable excipient.
6. The composition of claim 5 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of 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.
7. The composition of claim 1 , wherein the at least one 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.
8. The composition of claim 7 , wherein the 5′ untranslated region is heterologous to the coding region of the at least one mRNA.
9. The composition of claim 7 , wherein the 3′ untranslated region is heterologous to the coding region of the at least one mRNA.
10. The composition of claim 7 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the at least one mRNA.
11. The composition of claim 7 , wherein the mRNA comprises at least two stop codons.
12. The composition of claim 1 , wherein the coding region is selected from the group consisting of SEQ ID NO: 249789, 249797, 249800 and 249804.
13. A method of producing a Coagulation Factor XII comprising administering to a subject the composition of claim 1 .
14. The method of claim 13 , wherein the at least one mRNA of the composition comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.
15. The method of claim 14 , wherein the 5′ untranslated region is heterologous to the coding region of the at least one mRNA.
16. The method of claim 14 , wherein the 3′ untranslated region is heterologous to the coding region of the at least one mRNA.
17. The method of claim 14 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the at least one mRNA.
18. The method of claim 14 , wherein the mRNA comprises at least two stop codons.