MODIFIED POLYNUCLEOTIDES ENCODING PROGRAMMED CELL DEATH 1
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.
1 . A method of producing a protein of interest in a cell, tissue or organism comprising contacting said cell, tissue or organism with a nucleic acid encoding SEQ ID NO: 59118, wherein said nucleic acid comprises a coding region, said coding region having an altered G/C content as compared to the G/C content of the coding region comprising nucleotides 71-937 of SEQ ID NO: 23666.
2 . The method of claim 1 , wherein the coding region which has an altered G/C content is selected from the group of nucleic acid sequences consisting of SEQ ID NO: 94516, 129914, 165312, 200710 and 236108.
3 . The method of claim 2 , wherein the G/C content in the coding region is decreased as compared to the G/C content in the coding region of SEQ ID NO: 23666.
4 . The method of claim 3 , wherein the coding region with a decreased G/C content is selected from the group consisting of SEQ ID NO: 129914, 200710 and 236108.
5 . The method of claim 2 , wherein the G/C content in the coding region is increased as compared to the G/C content in the coding region of SEQ ID NO: 23666.
6 . The method of claim 5 , wherein the coding region with an increased G/C content is selected from the group consisting of SEQ ID NO: 94516 and 165312.
7 . The method of claim 2 , wherein the nucleic acid 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 method of claim 7 , wherein the 5′ untranslated region is heterologous to the coding region of the nucleic acid.
9 . The method of claim 7 , wherein the 3′ untranslated region is heterologous to the coding region of the nucleic acid.
10 . The method of claim 7 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the nucleic acid.
11 . The method of claim 7 , wherein the nucleic acid comprises at least two stop codons.
12 . A nucleic acid encoding SEQ ID NO: 59118, wherein said nucleic acid comprises a coding region, said coding region having an altered G/C content as compared to the G/C content of the coding region comprising nucleotides 71-937 of SEQ ID NO: 23666.
13 . The nucleic acid of claim 12 , wherein the coding region which has an altered G/C content is selected from the group of nucleic acid sequences consisting of SEQ ID NO: 94516, 129914, 165312, 200710 and 236108.
14 . The nucleic acid of claim 12 , wherein the G/C content in the coding region is decreased as compared to the G/C content in the coding region of SEQ ID NO: 23666.
15 . The nucleic acid of claim 14 , wherein the coding region with a decreased G/C content is selected from the group consisting of SEQ ID NO: 129914, 200710 and 236108.
16 . The nucleic acid of claim 12 , wherein the G/C content in the coding region is increased as compared to the G/C content in the coding region of SEQ ID NO: 23666.
17 . The nucleic acid of claim 16 , wherein the coding region with an increased G/C content is selected from the group consisting of SEQ ID NO: 94516 and 165312.
18 . The nucleic acid of claim 12 , wherein the nucleic acid comprises at least one untranslated region 5′ relative to the coding region and at least one untranslated region 3′ relative to the coding region.
19 . The nucleic acid of claim 18 , wherein the 5′ untranslated region is heterologous to the coding region of the nucleic acid.
20 . The nucleic acid of claim 18 , wherein the 3′ untranslated region is heterologous to the coding region of the nucleic acid.
21 . The nucleic acid of claim 18 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the nucleic acid.
22 . The nucleic acid of claim 18 , wherein the nucleic acid comprises at least two stop codons.
23 . A pharmaceutical composition comprising the codon optimized nucleic acid of claim 12 and a pharmaceutically acceptable excipient.
24 . The pharmaceutical composition of claim 23 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.