MODIFIED POLYNUCLEOTIDES ENCODING CASPASE 6
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of oncology-related polynucleotides, oncology-related primary transcripts and oncology-related 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: 5350, 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 25-639 of SEQ ID NO: 802.
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: 9847, 14335, 18823, 23311 and 27799.
3 . 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: 802.
4 . The method of claim 3 , wherein the coding region with an increased G/C content is selected from the group consisting of SEQ ID NO: 9847, 18823, 23311 and 27799.
5 . 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.
6 . The method of claim 5 , wherein the 5′ untranslated region is heterologous to the coding region of the nucleic acid.
7 . The method of claim 5 , wherein the 3′ untranslated region is heterologous to the coding region of the nucleic acid.
8 . The method of claim 5 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the nucleic acid.
9 . The method of claim 5 , wherein the nucleic acid comprises at least two stop codons.
10 . A nucleic acid encoding SEQ ID NO: 5350, 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 25-639 of SEQ ID NO: 802.
11 . The nucleic acid of claim 10 , 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: 9847, 14335, 18823, 23311 and 27799.
12 . The nucleic acid of claim 10 , 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: 802.
13 . The nucleic acid of claim 12 , wherein the coding region with an increased G/C content is selected from the group consisting of SEQ ID NO: 9847, 18823, 23311 and 27799.
14 . The nucleic acid of claim 10 , 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.
15 . The nucleic acid of claim 14 , wherein the 5′ untranslated region is heterologous to the coding region of the nucleic acid.
16 . The nucleic acid of claim 14 , wherein the 3′ untranslated region is heterologous to the coding region of the nucleic acid.
17 . The nucleic acid of claim 14 , wherein the 5′ untranslated region and the 3′ untranslated region are heterologous to the coding region of the nucleic acid.
18 . The nucleic acid of claim 14 , wherein the nucleic acid comprises at least two stop codons.
19 . A pharmaceutical composition comprising the codon optimized nucleic acid of claim 10 and a pharmaceutically acceptable excipient.
20 . The pharmaceutical composition of claim 19 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.