Optimized DNA cassettes for gene therapy

Abstract

Provided herein at least in part are sequences and constructs that can be used for gene therapy that can avoid or reduce interaction with said intracellular DNA-binding proteins and can enhance the potency, safety, efficiency, and / or effectiveness of gene therapy treatments, as well as related compositions and methods.

Description

[0001]OPTIMIZED DNA CASSETTES FOR GENE THERAPY RELATED APPLICATIONS This application claims the benefit of priority under 35 U.S.C. § 119(e) of U.S. Provisional Application Serial No. 63 / 676,456, filed on July 29, 2024, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION Gene therapy is a treatment modality that relies on the delivery of therapeutic genes, typically in the form of DNA, to cells for ideally stable multi-year expression to treat disease. Stable long-term expression generally requires efficient and effective transport of DNA into the cytoplasm, eventual translocation to the nucleus, and formation of a stable episome for long term gene expression, ideally in a silencing-resistant manner in some embodiments. Safe, efficient, and effective transport of DNA through the cytoplasm and avoidance of silencing in the nucleus generally requires the avoidance of, or a reduction in the level of, interaction of the DNA and a set of intracellular DNA-binding proteins. Provided are gene therapy cassette designs that can avoid or reduce interaction with said intracellular DNA-binding proteins to enhance the potency, safety, efficiency, and / or effectiveness of gene therapy treatments. SUMMARY OF THE INVENTION Stable long-term expression generally requires efficient and effective transport of DNA into the cytoplasm, eventual translocation to the nucleus, and formation of a stable episome for long term gene expression, ideally in a silencing-resistant manner in some embodiments. Typically, this can be achieved by viral vectors, which serve the function of transporting the DNA into the cytoplasm and then carrying the construct into the nucleus using viral and / or cellular machinery. However, since viral capsids and envelopes are not universally efficient, escape of genetic cargo to the cytoplasm can occur, which can trigger an innate immune response following interaction with intracytoplasmic DNA sensors. Moreover, once in the nucleus, interaction of specific DNA sequences and proteins can occur, leading to DNA methylation or recruitment of heterochromatin and generally epigenetic silencing of expression. Non-viral vectors rely on passive or active transport of genetic cargo to the nucleus following delivery to the cytoplasm. Since this process is oftentimes less efficient than active transport of viral vectors, the nucleic acids face an increased residence time in the cytoplasm. This increased residence time can enhance the frequency and extent of interaction with DNA sensors in the cytoplasm leading to inflammation, thereby reducing safety, efficiency, and potency of the treatment. Safe, efficient, and effective transport of DNA through the cytoplasm and avoidance of silencing in the nucleus generally requires the avoidance of, or a reduction in the level of, interaction of the DNA and a set of intracellular DNA-binding proteins. Provided herein are gene therapy cassette designs that can avoid or reduce interaction with said intracellular DNA-binding proteins and can enhance the potency, safety, efficiency, and / or effectiveness of gene therapy treatments. In one aspect is a DNA cassette for use in gene therapy treatment of mammalian pathologies, intended for delivery via viral or non-viral vectors, which has been optimized to exclude one or more sequences from a set of DNA sensor binding sites by base substitution to enhance hypoimmunogenicity and / or potency via modulation of inflammation, intracellular DNA sensing, or epigenetic regulation. In one embodiment of any one of the compositions or methods provided herein, the sequences are reactive to DNA sensors that activate the innate immune response. In one embodiment of any one of the compositions or methods provided herein, the sequences are reactive to DNA sensors that are intracellular DNA sensors. In one embodiment of any one of the compositions or methods provided herein, the sequences are reactive to DNA sensors capable of promoting epigenetic silencing. In one embodiment of any one of the compositions or methods provided herein, the sequences are bound by intracellular proteins, which can in turn activate the innate immune response. In one embodiment of any one of the compositions or methods provided herein, the sequences are bound by intracellular proteins, which can in turn activate intracellular DNA sensors. In one embodiment of any one of the compositions or methods provided herein, the sequences are bound by intracellular proteins, which can in turn promote formation of heterochromatin. In one embodiment of any one of the compositions or methods provided herein, the sequences are bound by intracellular proteins, which can in turn promote DNA methylation. In one embodiment of any one of the compositions or methods provided herein, the sequences are bound by intracellular proteins, which can in turn promote histone modifications that lead to a reduction in the level of gene expression. In one embodiment of any one of the compositions or methods provided herein, the sequences are TLR binding sites. In one embodiment of any one of the compositions or methods provided herein, the sequences are TLR9 binding sites. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of the cGAS-STING signaling pathway. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA Methyltransferases. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA methyltransferase 1. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA methyltransferase 3A. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA methyltransferase 3B. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA methyltransferase 3L. In one embodiment of any one of the compositions or methods provided herein, the sequences are binding sites of DNA methyltransferase 2. In one embodiment of any one of the compositions or methods provided herein, the sequences are DNA binding sites of SUV39H1, SUV39H2, SETDB1, MeCP2, SIRT1, CBX Proteins, Lamin B Receptor, Condensin Complex or proteins interacting with said proteins or protein complexes. In one embodiment of any one of the compositions or methods provided herein, the sequences mimic RNA binding sites of intracellular RNA sensors. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are double stranded DNA cassettes. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are partially double stranded DNA cassettes. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are single stranded DNA cassettes. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are linear DNA cassettes with or without covalently closed ends. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are circular DNA cassettes. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are DNA / RNA hybrids. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are DNA cassettes where at least some of the DNA has undergone chemical modification. In one embodiment of any one of the compositions or methods provided herein, the genetic cassettes are DNA-peptide or DNA-protein hybrids. In one embodiment of any one of the compositions or methods provided herein, the exclusion is a single nucleotide substitution or modification that prevents 100% homology with the original binding site sequence. In one embodiment of any one of the compositions or methods provided herein, the exclusion is a two-nucleotide substitution or modification that reduces homology with the original binding site sequence. In one embodiment of any one of the compositions or methods provided herein, the exclusion is a three-nucleotide substitution or modification that reduces homology with the original binding site sequence. In one embodiment of any one of the compositions or methods provided herein, the exclusion is a substitution of one to three nucleotides, that reduces homology with the original binding site sequence, without creating a new reactive sequence. In one embodiment of any one of the compositions or methods provided herein, the exclusion is a reduction in the total number of reactive sequences within the genetic cassette. In one embodiment of any one of the compositions or methods provided herein, the exclusion is complete elimination of 100% matching reactive sequences within the genetic cassette. In one embodiment of any one of the compositions or methods provided herein, the sequences are derived from any one or more Reactive Sequences listed herein, such as in the Examples. In one embodiment of any one of the compositions or methods provided herein, the viral vectors are comprised at least in part from at least a part of adeno-associated viruses, lentiviruses, retroviruses, herpes simplex viruses, adenoviruses, anneloviruses, enteroviruses, pox viruses, or other viruses known to be associated with humans or mammals. In one embodiment of any one of the compositions or methods provided herein, the nonviral vectors are comprised at least in part from at least a part of lipid nanoparticles, polymeric nanoparticles, metallic nanoparticles, liposomes, exosomes, virus like particles, cell membranes, lipids, or peptide complexes. In one embodiment of any one of the compositions or methods provided herein, the nonviral vectors are physical or chemical means of introducing genetic cassettes into mammalian cells. In one embodiment of any one of the compositions or methods provided herein, the reactive sequence is derived from at least 80% of any one of the sequences provided herein, such as listed in the Examples. In one embodiment of any one of the compositions or methods provided herein, the reactive sequence is capable of binding intracellular DNA sensors, components of proinflammatory complexes, or components of epigenetic silencing machinery. In one aspect is a method for constructing a therapeutic DNA sequence where original sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in the forward strand. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude that are present in the construct. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples. In one aspect is a method for constructing a therapeutic DNA sequence, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in the reverse strand. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in both forward and reverse strands. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in the coding region by identifying nucleotides that can be substituted in such a way that the highest frequency codon is selected for a given amino acid without affecting the amino acid encoded in the original consensus sequence. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in the coding region by identifying nucleotides that can be substituted in such a way that a codon with a similar frequency to the original codon is selected for a given amino acid without affecting the amino acid encoded in the original consensus sequence. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one aspect is a method for constructing a therapeutic DNA sequence, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude in the non-coding region by substituting nucleotides that are not essential to regulatory sequence functionality. In one embodiment, the sequence(s) to exclude is / are any one or more of the sequences provided herein, such as from the Examples, such as from Example 2. In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 22 is GCA and / or Codon # 23 is ACA and / or Codon # 25 is ATT and / or Codon # 37 is ACT and / or Codon # 52 is TCA and / or Codon # 56 is TTT and / or Codon # 65 is GTC and / or Codon # 66 is GGT and / or Codon # 70 is TAT and / or Codon # 73 is AGG and / or Codon # 81 is AGA and / or Codon # 83 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 12 is GTC and / or Codon # 14 is TCA and / or Codon # 16 is GCA and / or Codon # 22 is GCA and / or Codon # 23 is ACT and / or Codon # 24 is CCA and / or Codon # 25 is ATT and / or Codon # 27 is TCA and / or Codon # 33 is AGA and / or Codon # 37 is ACT and / or Codon # 38 is GCC and / or Codon # 39 is ACT and / or Codon # 40 is TGT and / or Codon # 41 is GCA and / or Codon # 42 is ACT and / or Codon # 44 is AGA and / or Codon # 46 is GCA and / or Codon # 52 is TCA and / or Codon # 53 is TCA and / or Codon # 56 is TTT and / or Codon # 57 is GGA and / or Codon # 58 is GCA and / or Codon # 61 is TCA and / or Codon # 62 is TCA and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 65 is GTT and / or Codon # 66 is GGA and / or Codon # 67 is TCA and / or Codon # 69 is ACT and / or Codon # 70 is TAT and / or Codon # 73 is AGA and / or Codon # 74 is AAT and / or Codon # 75 is GCA and / or Codon # 81 is AGA and / or Codon # 83 is CCA and / or Codon # 88 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 14 is TCC and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 37 is ACT and / or Codon # 51 is CAT and / or Codon # 63 is ACT and / or Codon # 65 is GTC and / or Codon # 74 is AAC and / or Codon # 75 is GCA and / or Codon # 80 is AAG and / or Codon # 81 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 14 is AGT and / or Codon # 15 is GTT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 37 is ACT and / or Codon # 44 is AGA and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 70 is TAT and / or Codon # 75 is GCT and / or Codon # 76 is GTT and / or Codon # 80 is AAG and / or Codon # 81 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 13 is CTC and / or Codon # 19 is CAC and / or Codon # 24 is CCT and / or Codon # 30 is GTT and / or Codon # 58 is GCT and / or Codon # 64 is AAC and / or Codon # 81 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 13 is CTC and / or Codon # 19 is CAC and / or Codon # 24 is CCT and / or Codon # 30 is GTT and / or Codon # 44 is AGA and / or Codon # 58 is GCT and / or Codon # 74 is AAT and / or Codon # 81 is AGA and / or Codon # 88 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 14 is TCC and / or Codon # 24 is CCT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 63 is ACT and / or Codon # 65 is GTT and / or Codon # 70 is TAT and / or Codon # 74 is AAC and / or Codon # 75 is GCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 12 is GTC and / or Codon # 14 is AGT and / or Codon # 15 is GTT and / or Codon # 24 is CCT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 40 is TGT and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 57 is GGA and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 65 is GTT and / or Codon # 70 is TAT and / or Codon # 75 is GCT and / or Codon # 76 is GTT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 18 is CTC and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 40 is TTT and / or Codon # 57 is ACT and / or Codon # 76 is AGT and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACC and / or Codon # 99 is AGT and / or Codon # 108 is GGT and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 137 is TCA and / or Codon # 156 is CCA and / or Codon # 162 is GCT and / or Codon # 165 is CTT and / or Codon # 174 is CTT and / or Codon # 188 is GTC and / or Codon # 195 is TCT and / or Codon # 205 is CCT and / or Codon # 207 is TAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 3 is TCA and / or Codon # 4 is GAT and / or Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 16 is TCA and / or Codon # 19 is GCA and / or Codon # 24 is GGA and / or Codon # 25 is GCA and / or Codon # 28 is GCT and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 32 is CCA and / or Codon # 34 is TCA and / or Codon # 35 is TCA and / or Codon # 36 is CCA and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 57 is ACT and / or Codon # 59 is GCA and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 68 is ACT and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCA and / or Codon # 73 is GCA and / or Codon # 76 is TCA and / or Codon # 77 is CCA and / or Codon # 79 is TCA and / or Codon # 85 is GCA and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACT and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 106 is CCA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 113 is TCA and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 122 is AGT and / or Codon # 124 is AGA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCA and / or Codon # 139 is GCA and / or Codon # 140 is CAT and / or Codon # 143 is CCA and / or Codon # 147 is CCA and / or Codon # 151 is TCA and / or Codon # 152 is CCA and / or Codon # 153 is CAT and / or Codon # 154 is AGA and / or Codon # 156 is CCA and / or Codon # 157 is GCA and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 161 is CCA and / or Codon # 162 is GCA and / or Codon # 163 is AGA and / or Codon # 165 is CTT and / or Codon # 166 is CCA and / or Codon # 168 is CCA and / or Codon # 171 is CCA and / or Codon # 172 is CCA and / or Codon # 173 is GCA and / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 177 is CCA and / or Codon # 178 is CCA and / or Codon # 182 is GCA and / or Codon # 183 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 190 is TCA and / or Codon # 191 is TCA and / or Codon # 193 is CCA and / or Codon # 194 is CTA and / or Codon # 195 is AGT and / or Codon # 199 is CCA and / or Codon # 200 is TCA and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 206 is TCA and / or Codon # 207 is TAT and / or Codon # 208 is GCA and / or Codon # 209 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACA and / or Codon # 10 is CAT and / or Codon # 16 is TCC and / or Codon # 32 is CCT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 73 is GCA and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 110 is CTC and / or Codon # 115 is CAC and / or Codon # 118 is CCT and / or Codon # 122 is AGT and / or Codon # 133 is AAC and / or Codon # 134 is GTC and / or Codon # 139 is GCG and / or Codon # 147 is CCT and / or Codon # 172 is CCT and / or Codon # 186 is CCG and / or Codon # 188 is GTC and / or Codon # 190 is TCG and / or Codon # 199 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACA and / or Codon # 10 is CAT and / or Codon # 16 is AGT and / or Codon # 19 is GCT and / or Codon # 32 is CCT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 73 is GCT and / or Codon # 77 is CCT and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 110 is CTC and / or Codon # 111 is TAT and / or Codon # 115 is CAC and / or Codon # 118 is CCT and / or Codon # 122 is AGT and / or Codon # 140 is CAT and / or Codon # 147 is CCT and / or Codon # 163 is AGA and / or Codon # 172 is CCT and / or Codon # 187 is GAT and / or Codon # 191 is TCT and / or Codon # 197 is GTT and / or Codon # 199 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 10 is CAT and / or Codon # 15 is GTC and / or Codon # 23 is TTG and / or Codon # 31 is ATA and / or Codon # 32 is CCT and / or Codon # 54 is GCT and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 91 is ATT and / or Codon # 94 is TTG and / or Codon # 100 is CGC and / or Codon # 105 is CGC and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 120 is GCA and / or Codon # 122 is AGT and / or Codon # 123 is TTC and / or Codon # 124 is CGC and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAC and / or Codon # 134 is GTT and / or Codon # 139 is GCG and / or Codon # 156 is CCT and / or Codon # 157 is GCT and / or Codon # 158 is CCA and / or Codon # 160 is GGA and / or Codon # 161 is CCT and / or Codon # 165 is TTG and / or Codon # 178 is CCA and / or Codon # 183 is CCT and / or Codon # 188 is GTC and / or Codon # 204 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 4 is GAT and / or Codon # 8 is TTT and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is TCT and / or Codon # 17 is GTT and / or Codon # 18 is TTG and / or Codon # 23 is TTG and / or Codon # 31 is ATA and / or Codon # 32 is CCT and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 68 is ACT and / or Codon # 72 is GCT and / or Codon # 73 is GCA and / or Codon # 77 is CCT and / or Codon # 91 is ATT and / or Codon # 94 is TTG and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 120 is GCA and / or Codon # 122 is AGT and / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 140 is CAT and / or Codon # 156 is CCT and / or Codon # 157 is GCT and / or Codon # 158 is CCA and / or Codon # 160 is GGA and / or Codon # 161 is CCT and / or Codon # 165 is TTG and / or Codon # 173 is GCA and / or Codon # 178 is CCA and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 191 is TCT and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 207 is TAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 8 is TTT and / or Codon # 12 is GGC and / or Codon # 16 is TCC and / or Codon # 28 is GCT and / or Codon # 39 is CAG and / or Codon # 40 is TTT and / or Codon # 51 is ACT and / or Codon # 68 is ACG and / or Codon # 72 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 118 is CCT and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 139 is GCG and / or Codon # 172 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 207 is TAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an FGF21 peptide encoded by a nucleic acid, such that Codon # 4 is GAT and / or Codon # 6 is ACA and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 12 is GGC and / or Codon # 16 is AGT and / or Codon # 28 is GCT and / or Codon # 39 is CAG and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 51 is ACT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 108 is GGA and / or Codon # 118 is CCT and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCT and / or Codon # 140 is CAT and / or Codon # 163 is AGA and / or Codon # 172 is CCT and / or Codon # 182 is GCA and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 191 is TCT and / or Codon # 207 is TAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 2 is AAA and / or Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 17 is GGT and / or Codon # 31 is CGA and / or Codon # 34 is TCA and / or Codon # 35 is GCA and / or Codon # 38 is GCA and / or Codon # 49 is GAA and / or Codon # 56 is GGA and / or Codon # 58 is TTT and / or Codon # 62 is TAT and / or Codon # 70 is CGG and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 91 is CGG and / or Codon # 95 is TTT and / or Codon # 97 is CGG and / or Codon # 101 is GGA and / or Codon # 103 is TTT and / or Codon # 107 is GTC and / or Codon # 108 is TCA and / or Codon # 132 is TTT and / or Codon # 138 is ATA and / or Codon # 145 is CGG and / or Codon # 149 is GGT and / or Codon # 157 is ACT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 2 is AAA and / or Codon # 3 is TCA and / or Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCA and / or Codon # 11 is TTT and / or Codon # 12 is GTC and / or Codon # 17 is GGT and / or Codon # 18 is TCA and / or Codon # 21 is AGA and / or Codon # 22 is TCA and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 31 is AGA and / or Codon # 32 is AGT and / or Codon # 34 is TCA and / or Codon # 35 is GCA and / or Codon # 36 is TCA and / or Codon # 38 is GCA and / or Codon # 40 is CCA and / or Codon # 42 is TCA and / or Codon # 44 is CCA and / or Codon # 48 is AAT and / or Codon # 52 is AGA and / or Codon # 54 is TCA and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 58 is TTT and / or Codon # 59 is ACT and / or Codon # 60 is TCA and / or Codon # 62 is TAT and / or Codon # 63 is TCA and / or Codon # 68 is AGT and / or Codon # 69 is AGA and / or Codon # 70 is AGA and / or Codon # 71 is GCA and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGA and / or Codon # 85 is AGA and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 89 is GCA and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 97 is AGA and / or Codon # 98 is CAT and / or Codon # 99 is GCA and / or Codon # 101 is GGA and / or Codon # 102 is ACT and / or Codon # 103 is TTT and / or Codon # 104 is ACT and / or Codon # 105 is TCA and / or Codon # 106 is GAT and / or Codon # 108 is TCA and / or Codon # 109 is TCA and / or Codon # 115 is GCA and / or Codon # 116 is GCA and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 121 is GCA and / or Codon # 127 is AGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 132 is TTT and / or Codon # 133 is CCA and / or Codon # 137 is GCA and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 144 is AGA and / or Codon # 145 is AGA and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 149 is GGA and / or Codon # 150 is AGT and / or Codon # 152 is TCA and / or Codon # 153 is GAT and / or Codon # 157 is ACT and / or Codon # 163 is GCA and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 174 is ACT and / or Codon # 177 is ACT and / or Codon # 179 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 34 is AGC and / or Codon # 49 is GAA and / or Codon # 51 is AAG and / or Codon # 53 is CAT and / or Codon # 59 is ACT and / or Codon # 60 is AGC and / or Codon # 75 is GTC and / or Codon # 83 is CGC and / or Codon # 91 is AGG and / or Codon # 95 is TTT and / or Codon # 99 is GCG and / or Codon # 105 is AGC and / or Codon # 106 is GAT and / or Codon # 127 is CGC and / or Codon # 137 is GCG and / or Codon # 138 is ATA and / or Codon # 164 is GCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon # 11 is TTT and / or Codon # 12 is GTC and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 31 is AGA and / or Codon # 34 is TCT and / or Codon # 38 is GCT and / or Codon # 42 is TCT and / or Codon # 48 is AAT and / or Codon # 51 is AAG and / or Codon # 52 is AGA and / or Codon # 53 is CAT and / or Codon # 59 is ACT and / or Codon # 60 is TCT and / or Codon # 69 is AGA and / or Codon # 70 is AGA and / or Codon # 75 is GTC and / or Codon # 83 is AGA and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 98 is CAT and / or Codon # 99 is GCT and / or Codon # 105 is TCT and / or Codon # 106 is GAT and / or Codon # 115 is GCT and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 127 is AGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 153 is GAT and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 177 is ACT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 12 is GTC and / or Codon # 26 is ACT and / or Codon # 32 is AGT and / or Codon # 44 is CCT and / or Codon # 48 is AAC and / or Codon # 68 is AGT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGG and / or Codon # 85 is CGC and / or Codon # 91 is CGG and / or Codon # 126 is GGG and / or Codon # 129 is AGA and / or Codon # 133 is CCT and / or Codon # 137 is GCG and / or Codon # 138 is ATA and / or Codon # 152 is AGC and / or Codon # 154 is GAG and / or Codon # 157 is ACT and / or Codon # 179 is CGC . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon # 12 is GTC and / or Codon # 14 is TTG and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 32 is AGT and / or Codon # 34 is TCT and / or Codon # 38 is GCT and / or Codon # 44 is CCT and / or Codon # 60 is TCT and / or Codon # 68 is AGT and / or Codon # 69 is AGA and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGG and / or Codon # 85 is AGA and / or Codon # 89 is GCA and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 97 is AGA and / or Codon # 105 is TCA and / or Codon # 106 is GAT and / or Codon # 115 is GCT and / or Codon # 126 is GGG and / or Codon # 127 is AGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 133 is CCT and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 152 is TCT and / or Codon # 154 is GAG and / or Codon # 157 is ACT and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 179 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 26 is ACT and / or Codon # 44 is CCT and / or Codon # 49 is GAA and / or Codon # 53 is CAT and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 62 is TAT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 84 is AAT and / or Codon # 95 is TTT and / or Codon # 99 is GCT and / or Codon # 133 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon # 11 is TTT and / or Codon # 12 is GTC and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 34 is TCT and / or Codon # 42 is TCT and / or Codon # 44 is CCT and / or Codon # 48 is AAT and / or Codon # 53 is CAT and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 60 is TCT and / or Codon # 62 is TAT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 84 is AAT and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 98 is CAT and / or Codon # 99 is GCT and / or Codon # 105 is TCT and / or Codon # 115 is GCT and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 133 is CCT and / or Codon # 136 is GTT and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 146 is CAT and / or Codon # 147 is GCT and / or Codon # 148 is GAT and / or Codon # 153 is GAT and / or Codon # 163 is GCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 18 is GCA and / or Codon # 20 is GCA and / or Codon # 21 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 29 is GGA and / or Codon # 31 is CCA and / or Codon # 32 is AGT and / or Codon # 33 is TCA and / or Codon # 34 is GGA and / or Codon # 35 is GCA and / or Codon # 36 is CCA and / or Codon # 37 is CCA and / or Codon # 38 is CCA and / or Codon # 39 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 32 is TCG . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 20 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 32 is TCC and / or Codon # 33 is TCT and / or Codon # 34 is GGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT and / or Codon # 8 is AGC and / or Codon # 10 is TAT and / or Codon # 20 is GCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT and / or Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 20 is GCT and / or Codon # 21 is GCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 10 is TAT and / or Codon # 12 is ATA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GGG peptide encoded by a nucleic acid, such that Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 12 is ATA and / or Codon # 20 is GCT and / or Codon # 29 is GGA and / or Codon # 33 is TCT and / or Codon # 34 is GGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 7 is TTT and / or Codon # 29 is TCA and / or Codon # 51 is CGG and / or Codon # 55 is GGA and / or Codon # 61 is TAT and / or Codon # 62 is TCA and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 91 is ATA and / or Codon # 94 is AGA and / or Codon # 97 is CGG and / or Codon # 129 is CTC and / or Codon # 138 is CTC . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 4 is ACT and / or Codon # 6 is ACT and / or Codon # 7 is TTT and / or Codon # 8 is GCA and / or Codon # 13 is TCA and / or Codon # 17 is GCA and / or Codon # 21 is GGG and / or Codon # 29 is TCA and / or Codon # 30 is GCA and / or Codon # 32 is CCA and / or Codon # 33 is TCA and / or Codon # 35 is CCA and / or Codon # 38 is TCA and / or Codon # 39 is CAT and / or Codon # 40 is GCA and / or Codon # 43 is TCA and / or Codon # 44 is TCA and / or Codon # 45 is CCT and / or Codon # 47 is CCT and / or Codon # 48 is AGA and / or Codon # 50 is CCA and / or Codon # 51 is AGA and / or Codon # 52 is TAT and / or Codon # 53 is GCA and / or Codon # 55 is GGA and / or Codon # 56 is ACT and / or Codon # 59 is TCA and / or Codon # 61 is TAT and / or Codon # 62 is TCA and / or Codon # 63 is ATT and / or Codon # 64 is GCT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 79 is GCT and / or Codon # 85 is AAT and / or Codon # 89 is CAT and / or Codon # 90 is AAT and / or Codon # 91 is ATT and / or Codon # 92 is ACT and / or Codon # 94 is AGA and / or Codon # 96 is GCA and / or Codon # 97 is AGA and / or Codon # 98 is GCA and / or Codon # 102 is GCA and / or Codon # 103 is TCA and / or Codon # 105 is GCA and / or Codon # 107 is AGA and / or Codon # 112 is GCA and / or Codon # 115 is CCT and / or Codon # 117 is TCA and / or Codon # 118 is TCA and / or Codon # 119 is CCA and / or Codon # 120 is GCA and / or Codon # 123 is CCA and / or Codon # 124 is TCA and / or Codon # 125 is GAT and / or Codon # 129 is CTC and / or Codon # 130 is AGA and / or Codon # 139 is GCA and / or Codon # 145 is ACT and / or Codon # 149 is AGA and / or Codon # 151 is AGA and / or Codon # 152 is TCA and / or Codon # 153 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 17 is GCA and / or Codon # 27 is CAC and / or Codon # 29 is AGC and / or Codon # 39 is CAT and / or Codon # 45 is CCT and / or Codon # 50 is CCT and / or Codon # 55 is GGA and / or Codon # 57 is TTT and / or Codon # 59 is AGC and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 107 is CGC and / or Codon # 112 is GCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 7 is TTT and / or Codon # 17 is GCT and / or Codon # 18 is GTT and / or Codon # 21 is GGG and / or Codon # 27 is CAC and / or Codon # 29 is TCT and / or Codon # 39 is CAT and / or Codon # 45 is CCT and / or Codon # 50 is CCT and / or Codon # 51 is AGA and / or Codon # 55 is GGA and / or Codon # 57 is TTT and / or Codon # 59 is TCT and / or Codon # 62 is TCT and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 85 is AAT and / or Codon # 89 is CAT and / or Codon # 107 is AGA and / or Codon # 112 is GCA and / or Codon # 124 is TCT and / or Codon # 130 is AGA and / or Codon # 151 is AGA and / or Codon # 153 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 16 is CTT and / or Codon # 17 is GCA and / or Codon # 20 is CTT and / or Codon # 36 is GTA and / or Codon # 47 is CCT and / or Codon # 53 is GCT and / or Codon # 61 is TAT and / or Codon # 89 is CAT and / or Codon # 112 is GCA and / or Codon # 130 is CGC and / or Codon # 146 is AAC . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 16 is CTT and / or Codon # 17 is GCA and / or Codon # 20 is CTT and / or Codon # 29 is TCT and / or Codon # 34 is CTA and / or Codon # 36 is GTT and / or Codon # 47 is CCT and / or Codon # 48 is AGA and / or Codon # 52 is TAT and / or Codon # 53 is GCT and / or Codon # 59 is TCT and / or Codon # 61 is TAT and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 79 is GCT and / or Codon # 85 is AAT and / or Codon # 89 is CAT and / or Codon # 96 is GCA and / or Codon # 97 is AGA and / or Codon # 107 is AGA and / or Codon # 112 is GCT and / or Codon # 113 is GTT and / or Codon # 124 is TCT and / or Codon # 130 is AGA and / or Codon # 138 is TTG and / or Codon # 146 is AAC and / or Codon # 153 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 19 is GGG and / or Codon # 34 is CTA and / or Codon # 35 is CCT and / or Codon # 53 is GCT and / or Codon # 61 is TAT and / or Codon # 74 is GTC and / or Codon # 85 is AAC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 115 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GIP peptide encoded by a nucleic acid, such that Codon # 19 is GGG and / or Codon # 20 is TTG and / or Codon # 21 is GGG and / or Codon # 29 is TCT and / or Codon # 34 is CTA and / or Codon # 35 is CCT and / or Codon # 52 is TAT and / or Codon # 53 is GCT and / or Codon # 59 is TCT and / or Codon # 61 is TAT and / or Codon # 62 is TCT and / or Codon # 63 is ATT and / or Codon # 74 is GTC and / or Codon # 89 is CAT and / or Codon # 115 is CCT and / or Codon # 124 is TCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 2 is ATA and / or Codon # 12 is ATA and / or Codon # 33 is GTT and / or Codon # 40 is CAT and / or Codon # 47 is AAT and / or Codon # 48 is AGT and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 65 is TTT and / or Codon # 66 is AGG and / or Codon # 70 is GGA and / or Codon # 72 is TTT and / or Codon # 76 is GTC and / or Codon # 77 is TCA and / or Codon # 104 is AGT and / or Codon # 107 is GGA and / or Codon # 110 is CCA and / or Codon # 129 is GGA and / or Codon # 132 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 2 is ATA and / or Codon # 3 is CCA and / or Codon # 4 is GCA and / or Codon # 8 is GCA and / or Codon # 12 is ATT and / or Codon # 13 is GTC and / or Codon # 16 is GCA and / or Codon # 21 is ACT and / or Codon # 23 is TCA and / or Codon # 24 is GAT and / or Codon # 27 is TCA and / or Codon # 31 is AGA and / or Codon # 32 is TCA and / or Codon # 33 is GTT and / or Codon # 34 is TCA and / or Codon # 40 is CAT and / or Codon # 47 is AAT and / or Codon # 48 is AGT and / or Codon # 51 is AGA and / or Codon # 56 is AGA and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 65 is TTT and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 70 is GGA and / or Codon # 71 is ACT and / or Codon # 72 is TTT and / or Codon # 73 is ACT and / or Codon # 74 is TCA and / or Codon # 75 is GAT and / or Codon # 77 is TCA and / or Codon # 78 is TCA and / or Codon # 84 is GCA and / or Codon # 85 is GCA and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 90 is GCA and / or Codon # 94 is GAT and / or Codon # 96 is AGA and / or Codon # 101 is CCT and / or Codon # 102 is AGA and / or Codon # 104 is TCA and / or Codon # 105 is AGA and / or Codon # 106 is AAT and / or Codon # 108 is CCA and / or Codon # 109 is GGT and / or Codon # 110 is CCA and / or Codon # 113 is GGA and / or Codon # 115 is AGA and / or Codon # 116 is AGA and / or Codon # 119 is AGA and / or Codon # 120 is AGA and / or Codon # 122 is AGA and / or Codon # 123 is CCT and / or Codon # 124 is AGA and / or Codon # 126 is TCA and / or Codon # 129 is GGA and / or Codon # 130 is CCT and / or Codon # 132 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 32 is TCC and / or Codon # 40 is CAT and / or Codon # 51 is CGC and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 66 is AGG and / or Codon # 75 is GAT and / or Codon # 104 is TCA and / or Codon # 107 is GGT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 23 is TCA and / or Codon # 24 is GAT and / or Codon # 27 is AGT and / or Codon # 28 is GTC and / or Codon # 31 is AGG and / or Codon # 32 is AGT and / or Codon # 33 is GTC and / or Codon # 34 is TCT and / or Codon # 40 is CAT and / or Codon # 51 is AGA and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 84 is GCT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 104 is TCA and / or Codon # 105 is AGG and / or Codon # 106 is AAT and / or Codon # 113 is GGA and / or Codon # 120 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 28 is GTG and / or Codon # 60 is CAA and / or Codon # 66 is AGG and / or Codon # 74 is TCA and / or Codon # 92 is TTG and / or Codon # 96 is CGC and / or Codon # 101 is CCG and / or Codon # 106 is AAC and / or Codon # 113 is GGA and / or Codon # 119 is CGC and / or Codon # 127 is CAT and / or Codon # 132 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 4 is GCA and / or Codon # 12 is ATA and / or Codon # 27 is TCT and / or Codon # 28 is GTC and / or Codon # 31 is AGA and / or Codon # 32 is TCT and / or Codon # 33 is GTT and / or Codon # 60 is CAA and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 92 is TTG and / or Codon # 96 is AGA and / or Codon # 98 is TTG and / or Codon # 102 is AGA and / or Codon # 108 is CCA and / or Codon # 113 is GGA and / or Codon # 116 is AGA and / or Codon # 119 is AGA and / or Codon # 120 is AGA and / or Codon # 127 is CAT and / or Codon # 132 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 3 is CCT and / or Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 32 is TCC and / or Codon # 40 is CAT and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 75 is GAT and / or Codon # 93 is GTC and / or Codon # 106 is AAC and / or Codon # 107 is GGT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 3 is CCT and / or Codon # 12 is ATT and / or Codon # 13 is GTC and / or Codon # 23 is TCT and / or Codon # 24 is GAT and / or Codon # 27 is AGT and / or Codon # 28 is GTC and / or Codon # 32 is AGT and / or Codon # 33 is GTC and / or Codon # 34 is TCT and / or Codon # 40 is CAT and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 84 is GCT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 94 is GAT and / or Codon # 108 is CCT and / or Codon # 113 is GGA and / or Codon # 120 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 18 is CTC and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 40 is TTT and / or Codon # 57 is ACT and / or Codon # 76 is AGT and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACC and / or Codon # 99 is AGT and / or Codon # 108 is GGT and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 137 is TCA and / or Codon # 156 is CCA and / or Codon # 162 is GCT and / or Codon # 165 is CTT and / or Codon # 174 is CTT and / or Codon # 188 is GTC and / or Codon # 195 is TCT and / or Codon # 205 is CCA and / or Codon # 208 is CGG and / or Codon # 212 is GGA and / or Codon # 214 is TTT and / or Codon # 218 is GTC and / or Codon # 219 is TCA and / or Codon # 246 is AGT and / or Codon # 249 is GGA and / or Codon # 252 is CCA and / or Codon # 271 is GGA and / or Codon # 274 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCA and / or Codon # 4 is GAT and / or Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 16 is TCA and / or Codon # 19 is GCA and / or Codon # 24 is GGA and / or Codon # 25 is GCA and / or Codon # 28 is GCT and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 32 is CCA and / or Codon # 34 is TCA and / or Codon # 35 is TCA and / or Codon # 36 is CCA and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 57 is ACT and / or Codon # 59 is GCA and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 68 is ACT and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCA and / or Codon # 73 is GCA and / or Codon # 76 is TCA and / or Codon # 77 is CCA and / or Codon # 79 is TCA and / or Codon # 85 is GCA and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACT and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 106 is CCA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 113 is TCA and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 122 is AGT and / or Codon # 124 is AGA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCA and / or Codon # 139 is GCA and / or Codon # 140 is CAT and / or Codon # 143 is CCA and / or Codon # 147 is CCA and / or Codon # 151 is TCA and / or Codon # 152 is CCA and / or Codon # 153 is CAT and / or Codon # 154 is AGA and / or Codon # 156 is CCA and / or Codon # 157 is GCA and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 161 is CCA and / or Codon # 162 is GCA and / or Codon # 163 is AGA and / or Codon # 165 is CTT and / or Codon # 166 is CCA and / or Codon # 168 is CCA and / or Codon # 171 is CCA and / or Codon # 172 is CCA and / or Codon # 173 is GCA and / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 177 is CCA and / or Codon # 178 is CCA and / or Codon # 182 is GCA and / or Codon # 183 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 190 is TCA and / or Codon # 191 is TCA and / or Codon # 193 is CCA and / or Codon # 194 is CTA and / or Codon # 195 is AGT and / or Codon # 199 is CCA and / or Codon # 200 is TCA and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 206 is TCA and / or Codon # 208 is AGG and / or Codon # 209 is CAT and / or Codon # 210 is GGA and / or Codon # 212 is GGA and / or Codon # 213 is ACT and / or Codon # 214 is TTT and / or Codon # 215 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 219 is TCA and / or Codon # 220 is TCA and / or Codon # 226 is GCA and / or Codon # 227 is GCA and / or Codon # 230 is TTT and / or Codon # 231 is ATT and / or Codon # 232 is GCA and / or Codon # 236 is GAT and / or Codon # 238 is AGA and / or Codon # 243 is CCT and / or Codon # 244 is AGA and / or Codon # 246 is TCA and / or Codon # 247 is AGA and / or Codon # 248 is AAT and / or Codon # 250 is CCA and / or Codon # 251 is GGT and / or Codon # 252 is CCA and / or Codon # 255 is GGA and / or Codon # 257 is AGA and / or Codon # 258 is AGA and / or Codon # 261 is AGA and / or Codon # 262 is AGA and / or Codon # 264 is AGA and / or Codon # 265 is CCT and / or Codon # 266 is AGA and / or Codon # 268 is TCA and / or Codon # 271 is GGA and / or Codon # 272 is CCT and / or Codon # 274 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is AGC and / or Codon # 6 is ACA and / or Codon # 15 is GTC and / or Codon # 16 is TCC and / or Codon # 40 is TTT and / or Codon # 54 is GCT and / or Codon # 60 is CAC and / or Codon # 69 is GTT and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 89 is GGA and / or Codon # 101 is TTC and / or Codon # 109 is GCC and / or Codon # 115 is CAC and / or Codon # 123 is TTC and / or Codon # 128 is TTG and / or Codon # 132 is TAT and / or Codon # 133 is AAC and / or Codon # 139 is GCG and / or Codon # 156 is CCT and / or Codon # 158 is CCT and / or Codon # 162 is GCT and / or Codon # 167 is TTG and / or Codon # 168 is CCT and / or Codon # 183 is CCT and / or Codon # 185 is CCG and / or Codon # 186 is CCT and / or Codon # 187 is GAT and / or Codon # 188 is GTT and / or Codon # 190 is TCT and / or Codon # 212 is GGA and / or Codon # 213 is ACT and / or Codon # 217 is GAT and / or Codon # 246 is TCA and / or Codon # 248 is AAC and / or Codon # 249 is GGT and / or Codon # 260 is TTC and / or Codon # 261 is CGT and / or Codon # 272 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 6 is ACA and / or Codon # 8 is TTT and / or Codon # 10 is CAC and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is AGT and / or Codon # 40 is TTT and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 60 is CAC and / or Codon # 69 is GTT and / or Codon # 71 is GGA and / or Codon # 73 is GCT and / or Codon # 77 is CCT and / or Codon # 89 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 115 is CAC and / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 128 is TTG and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 137 is TCT and / or Codon # 140 is CAT and / or Codon # 156 is CCT and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 162 is GCT and / or Codon # 163 is AGA and / or Codon # 167 is TTG and / or Codon # 168 is CCT and / or Codon # 183 is CCT and / or Codon # 186 is CCT and / or Codon # 187 is GAT and / or Codon # 188 is GTT and / or Codon # 190 is TCT and / or Codon # 191 is TCA and / or Codon # 209 is CAT and / or Codon # 210 is GGA and / or Codon # 212 is GGA and / or Codon # 213 is ACT and / or Codon # 217 is GAT and / or Codon # 230 is TTT and / or Codon # 231 is ATT and / or Codon # 246 is TCA and / or Codon # 247 is AGA and / or Codon # 260 is TTC and / or Codon # 261 is AGA and / or Codon # 262 is AGA and / or Codon # 272 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is AGC and / or Codon # 11 is TCT and / or Codon # 12 is GGC and / or Codon # 18 is CTC and / or Codon # 23 is TTG and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 44 is GTT and / or Codon # 57 is ACA and / or Codon # 61 is TTG and / or Codon # 63 is ATC and / or Codon # 64 is CGC and / or Codon # 69 is GTT and / or Codon # 73 is GCT and / or Codon # 85 is GCT and / or Codon # 90 is GTT and / or Codon # 94 is TTG and / or Codon # 99 is AGT and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 123 is TTC and / or Codon # 124 is CGC and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 146 is TTG and / or Codon # 153 is CAC and / or Codon # 166 is CCT and / or Codon # 174 is CTT and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 195 is AGT and / or Codon # 213 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 235 is GTT and / or Codon # 248 is AAC and / or Codon # 249 is GGT and / or Codon # 255 is GGA and / or Codon # 257 is CGG and / or Codon # 265 is CCT and / or Codon # 269 is CAT and / or Codon # 274 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 4 is GAT and / or Codon # 8 is TTT and / or Codon # 11 is TCT and / or Codon # 12 is GGC and / or Codon # 16 is TCT and / or Codon # 18 is TTG and / or Codon # 19 is GCA and / or Codon # 23 is TTG and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 44 is GTT and / or Codon # 45 is AGA and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 57 is ACA and / or Codon # 61 is TTG and / or Codon # 63 is ATC and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 69 is GTT and / or Codon # 73 is GCT and / or Codon # 85 is GCT and / or Codon # 90 is GTT and / or Codon # 94 is TTG and / or Codon # 95 is GGA and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 108 is GGA and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCA and / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 146 is TTG and / or Codon # 154 is AGA and / or Codon # 159 is AGA and / or Codon # 162 is GCA and / or Codon # 166 is CCT and / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 195 is AGT and / or Codon # 197 is GTT and / or Codon # 203 is AGA and / or Codon # 213 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 235 is GTT and / or Codon # 237 is GGA and / or Codon # 238 is AGA and / or Codon # 250 is CCT and / or Codon # 255 is GGA and / or Codon # 257 is AGA and / or Codon # 258 is AGA and / or Codon # 261 is AGA and / or Codon # 265 is CCT and / or Codon # 266 is AGA and / or Codon # 269 is CAT and / or Codon # 274 is CCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 10 is CAT and / or Codon # 15 is GTC and / or Codon # 16 is TCC and / or Codon # 30 is CCT and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 48 is TAC and / or Codon # 60 is CAC and / or Codon # 68 is ACG and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 106 is CCT and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 134 is GTT and / or Codon # 147 is CCT and / or Codon # 156 is CCT and / or Codon # 161 is CCT and / or Codon # 178 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 217 is GAT and / or Codon # 230 is TTT and / or Codon # 237 is GGA and / or Codon # 249 is GGT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 6 is ACA and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is AGT and / or Codon # 19 is GCT and / or Codon # 30 is CCT and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 48 is TAC and / or Codon # 51 is ACT and / or Codon # 60 is CAC and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 73 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 106 is CCT and / or Codon # 108 is GGA and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 133 is AAT and / or Codon # 137 is TCT and / or Codon # 147 is CCT and / or Codon # 156 is CCT and / or Codon # 161 is CCT and / or Codon # 168 is CCT and / or Codon # 175 is CCT and / or Codon # 178 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 191 is TCT and / or Codon # 210 is GGA and / or Codon # 217 is GAT and / or Codon # 226 is GCT and / or Codon # 230 is TTT and / or Codon # 237 is GGA and / or Codon # 238 is AGA and / or Codon # 248 is AAT and / or Codon # 250 is CCT and / or Codon # 261 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is GTC and / or Codon # 11 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GCA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 11 is TCA and / or Codon # 12 is TCA and / or Codon # 18 is GCA and / or Codon # 19 is GCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 24 is GCA and / or Codon # 30 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 5 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GCT and / or Codon # 5 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 22 is TTT and / or Codon # 23 is ATT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 18 is GCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 8 is TCT and / or Codon # 18 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 12 is ATT and / or Codon # 17 is ATT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 12 is ATT and / or Codon # 17 is ATT and / or Codon # 18 is GCT and / or Codon # 22 is GCT and / or Codon # 23 is TTT and / or Codon # 24 is GTC and / or Codon # 28 is ATT and / or Codon # 29 is GCA and / or Codon # 30 is GGA and / or Codon # 32 is CCA and / or Codon # 33 is AGT and / or Codon # 34 is TCA and / or Codon # 35 is GGA and / or Codon # 36 is GCA and / or Codon # 37 is CCA and / or Codon # 38 is CCA and / or Codon # 39 is CCA and / or Codon # 40 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 11 is TCT and / or Codon # 24 is GTC . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 8 is TCT and / or Codon # 11 is TCT and / or Codon # 24 is GTC and / or Codon # 28 is ATT and / or Codon # 29 is GCA and / or Codon # 30 is GGA and / or Codon # 34 is TCT and / or Codon # 35 is GGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 11 is TCT and / or Codon # 22 is GCG and / or Codon # 33 is TCG and / or Codon # 38 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 11 is TCT and / or Codon # 17 is ATT and / or Codon # 23 is TTT and / or Codon # 24 is GTC and / or Codon # 27 is TTG and / or Codon # 28 is ATT and / or Codon # 29 is GCT and / or Codon # 33 is TCC and / or Codon # 34 is TCT and / or Codon # 35 is GGA and / or Codon # 38 is CCA and / or Codon # 39 is CCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 10 is TAT and / or Codon # 11 is TCT and / or Codon # 24 is GTC . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 11 is TCT and / or Codon # 17 is ATT and / or Codon # 24 is GTC and / or Codon # 29 is GCT and / or Codon # 30 is GGA and / or Codon # 34 is TCT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is GTC and / or Codon # 11 is TCA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 11 is TCA and / or Codon # 12 is TCA and / or Codon # 18 is GCA and / or Codon # 19 is GCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 24 is GCA and / or Codon # 28 is GAT and / or Codon # 30 is AGA . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 5 is ACT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 18 is GCT and / or Codon # 23 is ATT and / or Codon # 28 is GAT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT . In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 22 is TTT. In one embodiment of any one of the compositions or methods provided herein, the therapeutic, construct, cassette or sequence is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GGA and / or Codon # 8 is TCT and / or Codon # 18 is GCT and / or Codon # 22 is TTT. In one embodiment of any one of the compositions or methods provided herein, the sequence(s) excluded, modified or replaced are any one or more of the sequences as provided herein. In one embodiment of any one of the compositions or methods provided herein, the sequence(s) used for modification or replacement are any one or more of the sequences as provided herein. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a base construct encoding glucagon. FIG. 2 shows results of sequences removed, for both the forward and reverse strands. FIG. 3 shows a construct encoding glucagon after optimization. FIG. 4 shows a base construct encoding fibroblast growth factor 21 (FGF21). FIG. 5 shows results of sequences removed. FIG. 6 shows an optimized FGF21 construct. FIG. 7 shows a base construct encoding apelin. FIG. 8 shows results of sequences removed. FIG. 9 shows an optimized apelin construct. DETAILED DESCRIPTION OF THE INVENTION Provided herein are genetic cassette structures that can be hypoimmunogenic, meaning that they have a reduced immune response relative to their alternatives for use in gene therapy treatment of disease, or augmentation of gene expression, or normal function of biological organisms. Provided herein are optimized genetic cassettes for use in gene therapy treatments. Moreover, provided herein are sequences that can be excluded (or optimized) to enable hypoimmunization of a DNA cassette, increasing transfection or transduction efficiency, potency, and / or safety of the treatment. Sequences that can be excluded include reactive sequences to intracellular DNA sensors, binding sites for proteins that enable epigenetic silencing or DNA methylation, or binding sites for proteins that enable downstream signaling cascades that promote inflammation, reduce or alter the level of gene expression, signal apoptosis, promote epigenetic silencing of the therapeutic construct, or otherwise adversely affect efficacy, potency, expression efficiency, or transfection or transduction efficiency of the therapy. Such exclusions or optimizations can include a substituted nucleotide along the disclosed sequence that creates a 1-base mismatch, two substituted nucleotides along the disclosed sequence that creates a 2-base mismatch, or multiple substituted nucleotides along the disclosed sequence that creates a multi-base mismatch, preferably in some embodiments without affecting the therapeutic activity of the delivered transgene. Such substitutions can occur in coding regions and non-critical non-coding regions. In the coding regions such substitutions can include the use of a high frequency codon as an alternative in the final therapeutic construct, the higher frequency in the target organism the better in some embodiments, without creating a perfect match to an immunogenic sequence. In general, the substituted sequences can have advantages over their consensus sequences in lower immunogenicity, higher expression, increase transfection or transduction efficiency in situations with potential exposure of the genetic cassette to intracytoplasmic DNA sensors, and / or increased durability and safety of treatment. As such, provided herein are sequences alternative to the consensus sequence, that can achieve intended therapeutic effect, but are optimized for enhanced hypoimmunogenicity, potency, efficiency, safety, and / or efficacy, and uses thereof. Similarly, provided herein are methods for optimizing assembled consensus sequences by analyzing the assembled therapeutic construct for the presence of sequences to exclude or optimize and substituting one or more bases to create optimized constructs, where the bases are substituted to create at least one and preferably two base mismatches with the listed sequences to exclude. In the coding region such substitutions can be attained by taking the highest frequency use codon from the species to be treated with the therapeutic gene therapy. Specifically, the final DNA construct may be searched for the sequences to exclude, sequences that are identified in the coding region can be modified to substitute nucleotides for at least one codon such that the encoded amino acid is unchanged, and a high frequency codon is selected, in some embodiments the highest frequency use for each codon in the sequence of interest, but such that there is not a 100% match to the sequences to exclude listed in Table 1 below. Table 1 More than one codon may be substituted in such a way to attain the final sequence of interest, which substitutes in such a way away from the consensus sequence, but creates mismatches in the potentially immunogenic or epigenetically active sequence. In some embodiments, such substitutions are performed in both the forward and reverse strand to maximally exclude the sequences listed in Table 1 above with sequences that have at least a 1-base mismatch or 2-bases of mismatch. Similarly, in non-coding regions, bases can be substituted to create 1-base mismatches or 2-base mismatches in both forward and reverse strands, such that in some embodiments the function of the non-coding region is unaffected (for example promoter activity). As a result of such optimizations, provided herein are DNA cassettes for use in gene therapy treatment, such as for mammalian pathologies, which can be used for delivery via viral or non-viral vectors, and which have been optimized to exclude one or more sequences from a set of herewithin disclosed sequences by at least one base substitution. More specifically, provided herein are DNA constructs or DNA cassettes for use in gene therapy, such as for treatment of mammalian disorders, conditions, pathologies, or generally insufficient gene expression, delivered via viral or non-viral vectors, which have been optimized for their original or consensus sequence components to exclude one or more sequences from a set of DNA sensor binding sites by one or more base substitution to enhance hypoimmunogenicity, transfection efficiency, expression efficiency, safety, efficacy, or potency of the treatment via modulation of inflammation, intracellular DNA sensing, or epigenetic regulation. In some embodiment the sequences to exclude from constructs via one or more nucleotide substitutions or base substitutions are sequences which are reactive to DNA sensors that activate the innate immune response or sequences which are reactive to DNA sensors that are intracellular DNA sensors or sequences which are reactive to DNA sensors capable of promoting epigenetic silencing or combinations of one or more similar or related pathways. In general sequences which can be analyzed for and excluded (or altered to prevent 100% homology) from the final therapeutic construct are sequences that are known to bind to proteins in a sequence-specific manner and in turn activate the innate immune response, or optionally specifically intracellular DNA sensors. In yet other embodiments the final construct is optimized for exclusion or substitution away from sequences that are bound by intracellular proteins, which can in turn promote formation of heterochromatin, or which are bound by intracellular proteins, which can in turn promote DNA methylation, or which are bound by intracellular proteins, which can in turn promote histone modifications that lead to a reduction in the level of gene expression. Exclusion can be performed by first assembling the final construct using original or consensus sequences, then analyzing the construct for presence of undesirable sequences and then substituting one or more bases, such that the functionality of the construct is generally unaffected, as in for example the same protein is encoded by the coding region, but the undesirable sequence is excluded based on 100% match homology. Such substitutions can take place in the form of 1 or more nucleotides away from the consensus sequence, or 1 or more nucleotides away from the original therapeutic sequence, or from a codon-optimized sequence. In some embodiments the sequences, which are targeted for optimization via nucleotide or base substitution are TLR binding sites, such as sites that bind TLR9 with high affinity, or other TLRs by similarity with RNA, or are CpG islands with 1 to 17 CpGs with or without flanking xCx sites, as in CGxCx (where X is any nucleotide or any DNA base). In yet other embodiments the sequences targeted for optimization are binding sites of proteins in the cGAS-STING signaling pathway. In other embodiments sequences that are targeted for optimization and can be excluded from the therapeutic construct are DNA sequences, which are binding sites of DNA Methyltransferases, as an example DNA Methyltransferase 3A, 3B, 3L, or 2, or proteins that form protein complexes that are known to bind DNA Methyltransferases or DNA methylating proteins. In yet other embodiments the sequences that can be excluded or optimized by base or nucleotide substitution are DNA binding sites of SUV39H1, SUV39H2, SETDB1, MeCP2, SIRT1, CBX Proteins, Lamin B Receptor, Condensin Complex or proteins interacting with said proteins or protein complexes. Similarly, sequences that are RNA binding sites of intracellular RNA sensors and innate immune defenses, or sequences or RNA that are known to elicit an innate immune response, or structured RNA sequences that can be mimicked by DNA sequences are additional sequences that can be targeted for optimization by base or nucleotide substitution. Such optimizations can be performed on partially formed or fully formed constructs, constructs that are eventually destined to become therapeutic DNA cassettes or serve as components of therapeutic formulations, and can generally be double-stranded DNA cassettes, single-stranded DNA cassettes, or partially double-stranded DNA cassettes, with or without RNA segments. The constructs can be linear with or without covalently closed ends, circular, or possess combinations of linear and circular segments with structural elements such as long terminal repeats or inverted terminal repeats, with or without RNA hybrids, with or without chemical modification to the nucleotide, nucleoside, or base component or any strand or both strands, and with or without covalently attached moieties on any segments or any bases or backbone of the DNA. The genetic cassettes can be destined for drug product production, can be the drug substances used in therapeutic formulations, or may be used for production of therapeutic formulations including drug products or drug substances. The cassettes can be coupled covalently or ionically or polyelectrolytically to peptides, proteins and form DNA-peptide or DNA-protein hybrids or be covalently or ionically coupled to polymers or oligomers and form DNA-polymer or DNA-oligomer hybrids. The constructs provided are generally constructs that have been optimized to exclude at least one instance of at least one immunogenic sequence or sequence that promotes epigenetic silencing of expression. In embodiments several such sequences are excluded, and in some embodiments all such sequences are excluded through nucleotide or base substitution. Exclusion can be defined as single nucleotide or base substitution or modification that removes or prevents 100% homology (meaning every nucleotide is identical with an undesirable sequence), with the original binding site sequence. In some embodiments, two-nucleotide substitutions are performed to the sequences to enable a further decrease in binding affinity between the DNA sensor or epigenetic silencing complex and the therapeutic genetic cassette. In some embodiments, three-nucleotide substitutions are performed to the sequences to enable a further decrease in binding affinity between the DNA sensor or epigenetic silencing complex and the therapeutic genetic cassette. However, whenever such substitutions are performed, it is beneficial in some embodiments to not affect regulatory sequence functionality or coding sequence to an extent that would reduce or eliminate therapeutic effect and such that a new reactive sequence is not created on the coding the non-coding strand. In some embodiments preferably an optimal level in the reduction of undesirable sequences on the forward and reverse strands and in some embodiments an at least 20% reduction in interacting sequences, with in other embodiments at least a 50% reduction in the number of interacting sequences undesirable in the final therapeutic construct. The optimized genetic constructs can be delivered with viral vectors, which can be comprised at least in part from at least a part of adeno-associated viruses, lentiviruses, retroviruses, herpes simplex viruses, adenoviruses, anneloviruses, enteroviruses, pox viruses, or other viruses known to be associated with humans or mammals. In other embodiments the optimized genetic constructs can be delivered with non-viral vectors which can be comprised at least in part from at least a part of lipid nanoparticles, polymeric nanoparticles, metallic nanoparticles, liposomes, exosomes, virus-like particles, cell membranes, lipids, or peptide complexes. In yet other embodiments non-viral vectors can be physical or chemical means of introducing genetic cassettes into mammalian cells or directly or indirectly into the nucleus. It is generally understood that reactive sequences that interact with intracellular DNA sensors that trigger an immune response, components of proinflammatory complexes or pathways, or nuclear DNA-binding proteins that result in epigenetic silencing of expression (or are generally associated with epigenetic silencing machinery whether it is targeting DNA directly or gene expression via histone modification or the creation of heterochromatin) are generally undesirable sequences and also interchangeably the reactive sequences that can be the target of the optimization. To enable replacement of sequences in original DNA constructs or from consensus sequences, or other therapeutic sequences, to exclude undesired sequences by substituting one or more nucleotides several methods may be used. One such method for constructing optimized therapeutic DNA sequences can involve obtaining an original sequence or a consensus sequence, analyzing it for the presence of undesirable sequences by identifying perfect matches in the forward and reverse strand and substituting one or more nucleotides to reduce the number of undesirable sequences. Another such method can involve analyzing the original therapeutic construct or consensus sequence containing construct for the presence of undesirable sequences that are 100% matching or have a 1-base mismatch and optimizing the construct by increasing the number of mismatches in at least some of the sequences by at least 1. Such optimizations can be performed on the forward and reverse strand, and preferably in some embodiments both on the forward and reverse strand, in such a way that the optimizations do not create new undesirable sequences. Methods for optimizing or designing out undesirable sequences can additionally include obtaining original or consensus sequences in preferably, in some embodiments, assembled form and modifying said sequences by substituting one or more nucleotides to reduce the number of sequences to exclude from the Table 1 above in the coding region by identifying nucleotides that can be substituted in such a way that the highest frequency codon is selected for a given amino acid without affecting the amino acid encoded in the original consensus sequence. In another embodiment, methods for constructing therapeutic DNA sequences can include the obtainment, analysis of, and modification of therapeutic DNA sequences by substituting one or more nucleotides to reduce the number of sequences to exclude from the Table 1 above in the non-coding region by substituting nucleotides that are not essential to regulatory sequence functionality. The sequences and methods for their optimization can optionally work in concert to enable synergistic or combinatorial effect on potency, hypoimmunogenicity, safety, efficacy, transfection or transduction efficiency, but may also be combined with other known means of reducing immunogenicity, increasing transgene expression, delivery, efficiency, safety, efficacy, or potency. It is understood that any one or more elements described herein can be combined with one or more other elements described herein or other means or methods of achieving the same or similar effect. The formulation, materials, genetic constructs, sequences, biological and chemical compositions, or methods of use may be varied by one skilled in the art, to the extent that the structures described herewithin perform the desired function and remain within the description provided herein. Various parts, components or characteristics may be used in combination, with or without modification by someone skilled in the art to achieve the desired functionality of the aforedescribed formulation. Moreover, all individual features and methods of use described herein, and each and every combination of two or more of such features and methods of use, are included within the scope of the present invention provided that these features and methods of use in such a combination are not mutually inconsistent. It is understood that certain portions or combinations of such portions can be varied by someone trained in the art while still achieving the main goal as provided herein. Finally, it is understood that the specific ranges provided in the current invention are not restrictive and are for example purposes, values outside of the specified ranges may be used to achieve the goal of the invention without modification to the proposed mechanistic principals. EXAMPLES Example 1 In this example a glucagon (GCG) coding therapeutic construct (a base construct with natural glucagon, FIG. 1) is optimized for hypoimmunogenicity with the original construct and optimized construct presented. Full FASTA sequence: CTAGCTGGCTTGTTGTCCACAACCATTAAACCTTAAAAGCTTTAAAAGCCTTAT ATATTCTTTTTTTTCTTATAAAACTTAAAACCTTAGAGGCTATTTAAGTTGCTGAT TTATATTAATTTTATTGTTCAAACATGAGAGCTTAGTACGTGAAACATGAGAGCT TAGTACATTAGCCATGAGAGCTTAGTACATTAGCCATGAGGGTTTAGTTCATTAA ACATGAGAGCTTAGTACATTAAACATGAGAGCTTAGTACATTAAACATGAGAGC TTAGTACATACTATCAACAGGTTGAACTGCTGATCTGTACAGTAGAATTGGTAA AGAGAGTTGTGTAAAATATTGAGTTCGCACATCTTGTTGTCTGATTATTGATTTT TGGCGAAACCATTTGATCATATGACAAGATGTGTATCTACCTTAACTTAATGATT TTGATAAAAATCATTAGGTACCCTGGGGACTTTCCAGCCTGGGGACTTTCCAGC TGGGACTTTCCAGGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACC GCCCAACGACCCCCGCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCC ATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATC AAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGC CCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCT GCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATT TTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCC AGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTG CGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGG CGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTC GCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCC GCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGC CCTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATG GTTGGTTGGTGGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCAC TTTTTTTCAGGTTGGGTTGGACGCGTCGCTAGCGCCACCATGAAAAGCATCTA CTTCGTGGCCGGCCTGTTCGTGATGCTGGTGCAAGGCAGCTGGCAGAGAAGC CTGCAGGACACCGAGGAAAAGTCCCGGAGCTTTTCTGCCAGCCAGGCCGACC CCCTGAGCGACCCTGATCAGATGAACGAGGACAAGAGACATTCTCAGGGCAC ATTCACCAGCGACTACAGCAAGTATCTGGACAGCAGAAGAGCCCAGGATTTTG TCCAGTGGCTGATGAACACCAAACGGAATCGGAACAACATCGCCAAGCGGCA CGACGAGTTCGAGCGGCACGCCGAGGGCACCTTCACAAGCGACGTGTCCAGC TACCTGGAAGGCCAAGCTGCTAAGGAATTCATTGCCTGGCTCGTGAAGGGCAG AGGAAGACGCGACTTCCCTGAGGAAGTGGCCATCGTGGAAGAGCTGGGAAG AAGGCACGCCGATGGCTCTTTTTCCGATGAGATGAATACCATCCTGGACAACCT GGCCGCTAGAGATTTCATCAACTGGCTGATCCAGACAAAGATCACCGACAGAA AGTAATGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGT GCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGA GGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGT GGGGCAGGACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGG GGACTGGGGACTTTCCAGCTGGGGACTTTCCAGCTGGGACTTTCCAGGAGA CBh promoter: CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCC GCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGC CAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTGTG CCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGT CATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCAT CTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTG CAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGC GGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATC AGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCG GCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTT CGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACT GACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCT GTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTA TTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGG Glucagon: ATGAAAAGCATCTACTTCGTGGCCGGCCTGTTCGTGATGCTGGTGCAAGGCAG CTGGCAGAGAAGCCTGCAGGACACCGAGGAAAAGTCCCGGAGCTTTTCTGCC AGCCAGGCCGACCCCCTGAGCGACCCTGATCAGATGAACGAGGACAAGAGAC ATTCTCAGGGCACATTCACCAGCGACTACAGCAAGTATCTGGACAGCAGAAGA GCCCAGGATTTTGTCCAGTGGCTGATGAACACCAAACGGAATCGGAACAACAT CGCCAAGCGGCACGACGAGTTCGAGCGGCACGCCGAGGGCACCTTCACAAGC GACGTGTCCAGCTACCTGGAAGGCCAAGCTGCTAAGGAATTCATTGCCTGGCT CGTGAAGGGCAGAGGAAGACGCGACTTCCCTGAGGAAGTGGCCATCGTGGAA GAGCTGGGAAGAAGGCACGCCGATGGCTCTTTTTCCGATGAGATGAATACCAT CCTGGACAACCTGGCCGCTAGAGATTTCATCAACTGGCTGATCCAGACAAAGA TCACCGACAGAAAGTAA Glucagon protein sequence: MKSIYFVAGLFVMLVQGSWQRSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHS QGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVS SYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLA ARDFINWLIQTKITDRK Bovine growth hormone polyadenylation sequence: CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTT GACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTG CATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAG GACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGA Following optimization, the number of sequences in the forward strand dropped from 41 to 8, and the number of sequences in the reverse strand dropped from 43 to 4 and the construct produced >2.5x in expression (FIG. 2).The construct after optimization is shown in FIG. 3. Optimized glucagon: ATGAAAAGCATCTACTTTGTTGCTGGCCTGTTTGTGATGCTGGTGCAAGGCAG CTGGCAGAGAAGCCTGCAGGACACAGAGGAAAAGTCAAGGTCCTTTTCTGCC AGCCAGGCTGACCCCCTGTCTGACCCTGATCAGATGAATGAAGACAAGAGAC ACAGCCAGGGGACCTTTACCTCTGACTACTCCAAGTATCTGGACAGCAGAAGA GCCCAGGATTTTGTCCAGTGGCTGATGAACACCAAAAGAAATAGGAACAACAT TGCCAAGAGGCATGATGAGTTTGAAAGGCATGCTGAGGGCACCTTCACATCTG ATGTAAGCAGCTACCTGGAAGGCCAAGCTGCTAAGGAATTTATAGCCTGGCTG GTCAAGGGCAGAGGAAGAAGGGACTTCCCTGAGGAAGTGGCGATTGTTGAAG AGCTTGGCAGAAGGCATGCTGATGGCTCTTTTAGCGATGAGATGAATACCATCC TGGACAACCTGGCTGCTAGAGATTTCATCAACTGGCTGATCCAGACAAAGATC ACAGACAGAAAGTAA Example 2 In this example, a base construct contains a CBh promoter, the full-length gene encoding fibroblast growth factor 21 (FGF21), and a bovine growth hormone polyadenylation sequence on a nanoplasmid backbone (FIG. 4). Full FASTA sequence: CTAGCTGGCTTGTTGTCCACAACCATTAAACCTTAAAAGCTTTAAAAGCCTTAT ATATTCTTTTTTTTCTTATAAAACTTAAAACCTTAGAGGCTATTTAAGTTGCTGAT TTATATTAATTTTATTGTTCAAACATGAGAGCTTAGTACGTGAAACATGAGAGCT TAGTACATTAGCCATGAGAGCTTAGTACATTAGCCATGAGGGTTTAGTTCATTAA ACATGAGAGCTTAGTACATTAAACATGAGAGCTTAGTACATTAAACATGAGAGC TTAGTACATACTATCAACAGGTTGAACTGCTGATCTGTACAGTAGAATTGGTAA AGAGAGTTGTGTAAAATATTGAGTTCGCACATCTTGTTGTCTGATTATTGATTTT TGGCGAAACCATTTGATCATATGACAAGATGTGTATCTACCTTAACTTAATGATT TTGATAAAAATCATTAGGTACCCTGGGGACTTTCCAGCCTGGGGACTTTCCAGC TGGGACTTTCCAGGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACC GCCCAACGACCCCCGCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCC ATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATC AAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGC CCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCT GCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATT TTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCC AGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTG CGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGG CGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTC GCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCC GCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGC CCTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATG GTTGGTTGGTGGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCAC TTTTTTTCAGGTTGGGTTGGACGCGTCGCTAGCGCCACCATGGACAGCGACGA GACAGGCTTCGAGCACAGCGGCCTGTGGGTGTCCGTGCTGGCCGGCCTGCTT CTGGGCGCCTGCCAGGCCCACCCCATCCCTGATTCCAGCCCTCTGCTGCAGTT CGGCGGCCAGGTGCGGCAGCGGTACCTGTACACCGACGACGCCCAGCAGACC GAGGCCCATCTGGAAATCAGAGAGGACGGAACAGTGGGCGGAGCTGCTGATC AGTCTCCTGAGTCCCTGCTGCAACTGAAGGCCCTGAAGCCTGGCGTGATCCAG ATCCTGGGAGTGAAAACCAGCAGATTCCTGTGCCAAAGACCTGACGGCGCCC TGTACGGCTCTCTGCACTTCGACCCTGAAGCCTGTAGCTTCAGGGAACTGCTG CTGGAAGATGGATATAACGTGTACCAGAGCGAGGCCCACGGCCTGCCTCTGCA CCTGCCTGGCAACAAGTCTCCCCACCGGGACCCCGCCCCTAGAGGCCCTGCCA GATTTCTCCCACTGCCTGGACTGCCCCCCGCTCTGCCTGAGCCCCCCGGCATCC TGGCTCCACAGCCTCCAGACGTGGGCAGCTCTGATCCTCTGAGCATGGTCGGC CCCAGCCAGGGCAGAAGCCCTAGCTACGCCAGCTAATGACTGTGCCTTCTAGT TGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGT GCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTG AGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGG AGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGACTGGGGACTTTCCAGCTG GGGACTTTCCAGCTGGGACTTTCCAGGAGA CBh promoter: CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCC GCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGC CAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTGTG CCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGT CATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCAT CTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTG CAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGC GGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATC AGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCG GCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTT CGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACT GACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCT GTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTA TTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGG FGF21: ATGGACAGCGACGAGACAGGCTTCGAGCACAGCGGCCTGTGGGTGTCCGTGC TGGCCGGCCTGCTTCTGGGCGCCTGCCAGGCCCACCCCATCCCTGATTCCAGC CCTCTGCTGCAGTTCGGCGGCCAGGTGCGGCAGCGGTACCTGTACACCGACG ACGCCCAGCAGACCGAGGCCCATCTGGAAATCAGAGAGGACGGAACAGTGG GCGGAGCTGCTGATCAGTCTCCTGAGTCCCTGCTGCAACTGAAGGCCCTGAAG CCTGGCGTGATCCAGATCCTGGGAGTGAAAACCAGCAGATTCCTGTGCCAAAG ACCTGACGGCGCCCTGTACGGCTCTCTGCACTTCGACCCTGAAGCCTGTAGCT TCAGGGAACTGCTGCTGGAAGATGGATATAACGTGTACCAGAGCGAGGCCCAC GGCCTGCCTCTGCACCTGCCTGGCAACAAGTCTCCCCACCGGGACCCCGCCCC TAGAGGCCCTGCCAGATTTCTCCCACTGCCTGGACTGCCCCCCGCTCTGCCTG AGCCCCCCGGCATCCTGGCTCCACAGCCTCCAGACGTGGGCAGCTCTGATCCT CTGAGCATGGTCGGCCCCAGCCAGGGCAGAAGCCCTAGCTACGCCAGCTAA FGF21 protein sequence: MDSDETGFEHSGLWVSVLAGLLLGACQAHPIPDSSPLLQFGGQVRQRYLYTDDA QQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGA LYGSLHFDPEACSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRGPARF LPLPGLPPALPEPPGILAPQPPDVGSSDPLSMVGPSQGRSPSYAS Bovine growth hormone polyadenylation sequence: CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTT GACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTG CATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAG GACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGA The construct above was scanned for the following sequences, which were excluded by replacing at least one nucleotide with an alternative nucleotide to enable at least one, and ideally 2-mismatches with the original sequence. Both the forward and reverse strands were optimized in this way. In the coding region, alternative codons with high frequency of use in the human genome were selected (the higher the better, but avoiding a perfect match). In the non-coding region all sequences were optimized except those nucleotides affecting promoter, enhancer, polyA signal, termination, or other required regulatory sequences. Table 3: Following optimization, the number of sequences in the forward strand dropped from 50 to 9, and the number of sequences in the reverse strand dropped from 44 to 9 and the construct produced 2.2x in expression (FIG. 5). The optimized construct is shown in FIG. 6. Optimized FGF21: ATGGACTCTGATGAGACAGGGTTTGAACATTCTGGCCTGTGGGTGTCTGTGCT GGCTGGCCTGCTTCTGGGGGCCTGCCAGGCCCACCCCATCCCTGATTCCAGCC CTCTGCTGCAGTTTGGAGGCCAGGTGAGGCAGAGGTACCTGTACACAGATGAT GCCCAGCAGACAGAGGCCCACCTCGAGATCAGAGAAGATGGCACAGTTGGTG GGGCTGCTGATCAGTCTCCTGAGTCCCTGCTGCAACTGAAGGCCCTGAAGCCC GGAGTCATCCAGATCCTGGGAGTGAAAACCAGCAGATTCCTGTGCCAAAGAC CTGATGGAGCCCTGTATGGGTCTCTGCACTTTGATCCTGAAGCCTGTAGCTTCA GGGAACTGCTGCTGGAAGATGGATACAATGTCTACCAGTCTGAGGCGCATGGA CTGCCTCTGCACCTGCCTGGCAACAAGTCTCCCCACAGGGACCCTGCTCCTAG AGGCCCTGCCAGATTTCTGCCTCTGCCTGGACTGCCCCCTGCACTGCCTGAGC CGCCTGGGATCCTGGCTCCCCAACCTCCAGATGTTGGCAGCTCTGATCCTCTG AGCATGGTGGGCCCCAGCCAGGGCAGAAGCCCTAGCTATGCTTCCTAA Example 3 In this example, a base construct contains a CBh promoter, the full-length gene encoding apelin, and a bovine growth hormone polyadenylation sequence on a nanoplasmid backbone (FIG. 7). Full FASTA sequence: CTAGCTGGCTTGTTGTCCACAACCATTAAACCTTAAAAGCTTTAAAAGCCTTAT ATATTCTTTTTTTTCTTATAAAACTTAAAACCTTAGAGGCTATTTAAGTTGCTGAT TTATATTAATTTTATTGTTCAAACATGAGAGCTTAGTACGTGAAACATGAGAGCT TAGTACATTAGCCATGAGAGCTTAGTACATTAGCCATGAGGGTTTAGTTCATTAA ACATGAGAGCTTAGTACATTAAACATGAGAGCTTAGTACATTAAACATGAGAGC TTAGTACATACTATCAACAGGTTGAACTGCTGATCTGTACAGTAGAATTGGTAA AGAGAGTTGTGTAAAATATTGAGTTCGCACATCTTGTTGTCTGATTATTGATTTT TGGCGAAACCATTTGATCATATGACAAGATGTGTATCTACCTTAACTTAATGATT TTGATAAAAATCATTAGGTACCCTGGGGACTTTCCAGCCTGGGGACTTTCCAGC TGGGACTTTCCAGGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACC GCCCAACGACCCCCGCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCC ATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATC AAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGC CCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGT ACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCT GCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATT TTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCC AGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTG CGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGG CGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTC GCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCC GCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGC CCTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATG GTTGGTTGGTGGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCAC TTTTTTTCAGGTTGGGTTGGACGCGTCGCTAGCGCCACCATGAACCTGAGACT GTGTGTGCAGGCCCTGCTGCTGCTGTGGCTGTCCCTGACCGCCGTGTGCGGCG GATCTCTGATGCCTCTGCCTGATGGCAACGGCCTCGAGGACGGAAATGTGCGG CACCTGGTCCAACCTAGAGGCAGCAGAAACGGCCCAGGCCCTTGGCAGGGCG GCAGACGGAAGTTCCGGAGACAGCGCCCCAGACTGAGCCACAAGGGCCCTAT GCCCTTCTAATGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCC CCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAA AATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGT GGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAG GCTGGGGACTGGGGACTTTCCAGCTGGGGACTTTCCAGCTGGGACTTTCCAG GAGA CBh promoter: CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCC GCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGG TGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGC CAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTGTG CCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGT CATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCAT CTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTG CAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGC GGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATC AGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCG GCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTT CGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACT GACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCT GTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTA TTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGG Apelin: ATGAACCTGAGACTGTGTGTGCAGGCCCTGCTGCTGCTGTGGCTGTCCCTGAC CGCCGTGTGCGGCGGATCTCTGATGCCTCTGCCTGATGGCAACGGCCTCGAGG ACGGAAATGTGCGGCACCTGGTCCAACCTAGAGGCAGCAGAAACGGCCCAGG CCCTTGGCAGGGCGGCAGACGGAAGTTCCGGAGACAGCGCCCCAGACTGAGC CACAAGGGCCCTATGCCCTTCTAA Apelin protein sequence: MNLRLCVQALLLLWLSLTAVCGGSLMPLPDGNGLEDGNVRHLVQPRGSRNGPGP WQGGRRKFRRQRPRLSHKGPMPF Bovine growth hormone polyadenylation sequence: CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTT GACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTG CATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAG GACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGA Following optimization, the number of sequences in the forward strand dropped from 17 to 7, and the number of sequences in the reverse strand dropped from 22 to 4 and expression increased by 3.2x (FIG. 8). The optimized construct is shown in FIG. 9. Optimized apelin: ATGAACCTGAGACTCTGTGTCCAGGCCCTGCTGCTCCTCTGGCTGTCCCTGAC AGCTGTCTGTGGGGGATCTCTGATGCCTCTGCCTGATGGCAATGGACTGGAAG ATGGCAACGTGAGGCACCTGGTCCAACCTAGAGGCAGCAGAAATGGACCAGG CCCTTGGCAGGGAGGCAGAAGAAAGTTCAGGAGACAGAGGCCCAGACTGAG CCACAAGGGCCCTATGCCCTTCTAA Example 4: In the present example, a hypoimmunogenization strategy is applied to therapeutic transgenes encoding Amino Acid (AA) sequences from Table 2 below. A GLP-1 receptor agonist or a modified GLP-1 receptor agonist (mGLP-1), a dual GIP / GLP receptor agonist with stabilizing modifications (mGLP-1 / GIP), a GIP receptor mono-agonist peptide (GIP), a glucagon receptor agonist peptide (GCG), a glucagon / GLP-1 / GIP triple receptor agonist peptide (GGG), an amylin peptide (Amylin), an FGF21, a GLP- 1 / FGF21 / Apelin triple agonist, and a GLP-1 / Apelin / PTHY triple agonist are delivered in the form of nucleic acids encoding the peptide / protein amino acid sequence. Four separate codon optimization strategies are applied to the nucleic acid sequence, which is initially derived from a nucleic acid database or reverse translation. The first strategy utilizes the highest frequency codon tables for homo sapiens, the remaining strategies use 1 of 3 codon optimizers which optimize the usage of codons using codon usage bias adaptation and / or GC content optimization, and / or mRNA secondary structure optimization, and / or avoidance of RNA instability motifs, and / or avoiding of repeat and rare codons, and / or elimination of restriction sites, and / or removal of cryptic PolyA sites, splice cites, and miRNA target sites (Strategy 1 through Strategy 3). Finally, the DNA sequences are hypoimmunogenized by switching the optimized codons with hypoimmunogenic codons such that the presence or frequency of immunogenic protein binding sequences is eliminated or reduced respectively. The hypoimmunogenization can be performed with or without the exclusion of CpG sequences, known for their reactivity with TLR9. The resulting DNA sequence is reported for each hypoimmunogenization strategy via a reference number in the column ‘DNA Sequence Number’, and can be optionally introduced into a vector for the treatment of human or veterinary pathologies. The DNA sequence can be utilized in its entirety or by selecting specific codons for replacement relative to the original sequence. The vector may be delivered by a Lipid Nanoparticle formulation and administered via a subcutaneous injection for local transgene administration, and systemic therapeutic effect following protein expression, secretion, and biodistribution. >GLP-1 HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG >mGLP-1 HGEGTFTSDVSSYLEGQAAQEFIAWLVDGRG >mGLP-1 / GIP YGEGTFTSDYSIGLDKIAQKKAFVQWLIAGGPSSGAPPPS >GIP MVATKTFALLLLSLFLAVGLGEKKEGHFSALPSLPVGSHAKVSSPQPRGPRYAEGT FISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQREARALELASQANRKEE EAVEPQSSPAKNPSDEDLLRDLLIQELLACLLDQTNLCRLRSR >GCG MKSIYFVAGLFVMLVQGSWQRSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHS QGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVS SYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLA ARDFINWLIQTKITDRK >GGG YGQGTFTSDYSIILDKKAQAAFIEYLLEGGPSSGAPPPS >Amylin MGILKLQVFLIVLSVALNHLKATPIESHQVEKRKCNTATCATQRLANFLVHSSNNF GAILSSTNVGSNTYGKRNAVEVLKREPLNYLPL >FGF21 MDSDETGFEHSGLWVSVLAGLLLGACQAHPIPDSSPLLQFGGQVRQRYLYTDDA QQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGA LYGSLHFDPEACSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRGPARF LPLPGLPPALPEPPGILAPQPPDVGSSDPLSMVGPSQGRSPSYAS >GLP-1 / FGF21 / Apelin MDSDETGFEHSGLWVSVLAGLLLGACQAHPIPDSSPLLQFGGQVRQRYLYTDDA QQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGA LYGSLHFDPEACSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRGPARF LPLPGLPPALPEPPGILAPQPPDVGSSDPLSMVGPSQGRSPSYRHGEGTFTSDVSSY LEGQAAQEFIAWLVDGRGLVQPRGSRNGPGPWQGGRRKFRRQRPRLSHKGPMPF >GLP-1 / Apelin / PTHY MIPAKDMAKVMIVMLAICFLTKSDGKSVKKRSVSEIQLMHNLGKHLNSMERVEW LRKKLQDVHNFRHGEGTFTSDVSSYLEGQAAQEFIAWLVDGRGLVQPRGSRNGP GPWQGGRRKFRRQRPRLSHKGPMPF Table 2: DNA Sequences following Hypoimmunogenization, via reference number to Table 2 above: 1 CACGCGGAGGGCACGTTCACGTCGGACGTGTCGTCGTACCTGGAGGGCCA GGCGGCGAAGGAGTTCATCGCGTGGCTGGTGAAGGGCCGCGGC 2 CACGCCGAAGGCACATTTACAAGCGACGTGTCCAGCTACCTGGAGGGACA GGCAGCCAAAGAGTTCATCGCCTGGCTGGTGAAAGGCAGAGGC 3 CATGCCGAGGGCACCTTTACCAGTGATGTATCATCCTATTTGGAGGGACAA GCGGCCAAAGAGTTTATTGCTTGGCTGGTGAAGGGAAGAGGC 4 CATGCCGAAGGCACCTTTACCAGCGATGTGAGCAGCTACCTGGAGGGCCA GGCCGCCAAGGAATTCATCGCCTGGCTGGTGAAGGGCAGGGGC 5 CACGCGGAGGGAACGTTTACGTCGGACGTCTCATCGTACCTGGAGGGCCA GGCGGCGAAGGAGTTCATCGCGTGGCTGGTGAAGGGCCGCGGC 6 CACGCTGAAGGCACTTTTACATCAGATGTGTCCAGCTACCTGGAGGGACAG GCAGCCAAAGAGTTCATCGCCTGGCTGGTGAAAGGCAGAGGC 7 CATGCTGAGGGCACCTTTACCAGTGATGTATCATCCTATTTGGAGGGACAAG CGGCCAAAGAGTTTATTGCTTGGCTGGTGAAGGGAAGAGGC 8 CATGCTGAAGGCACCTTTACCAGCGATGTGAGCAGCTACCTGGAGGGCCA GGCCGCCAAGGAATTCATCGCCTGGCTGGTGAAGGGCAGGGGC 9 CATGCAGAGGGAACTTTTACTTCAGATGTGTCATCATACCTGGAGGGCCAG GCAGCAAAGGAGTTTATTGCATGGCTGGTGAAGGGCAGAGGC 10 CATGCTGAAGGCACTTTTACATCAGATGTGTCCAGCTACCTGGAGGGACAG GCAGCCAAAGAGTTTATTGCCTGGCTGGTGAAAGGCAGAGGC 11 CATGCTGAGGGCACCTTTACCAGTGATGTATCATCCTATTTGGAGGGACAAG CAGCCAAAGAGTTTATTGCTTGGCTGGTGAAGGGAAGAGGC 12 CATGCTGAAGGCACCTTTACCTCTGATGTGAGCAGCTACCTGGAGGGCCAG GCTGCCAAGGAATTTATTGCCTGGCTGGTGAAGGGCAGGGGC 13 CACGGCGAGGGCACGTTCACGTCGGACGTGTCGTCGTACCTGGAGGGCCA GGCGGCGCAGGAGTTCATCGCGTGGCTGGTGGACGGCCGCGGC 14 CATGGAGAGGGCACATTCACATCTGATGTGAGCTCTTACCTGGAAGGACAG GCCGCCCAGGAGTTTATCGCCTGGCTGGTGGACGGCAGAGGC 15 CATGGGGAGGGAACATTTACGTCTGATGTTAGCTCCTACCTGGAAGGACAG GCTGCTCAAGAATTTATTGCTTGGCTGGTGGATGGAAGGGGC 16 CACGGCGAAGGCACCTTTACCAGCGATGTGAGCAGCTACCTGGAAGGCCA GGCCGCCCAGGAATTCATTGCCTGGCTGGTGGATGGCAGGGGC 17 CACGGCGAGGGAACGTTTACGTCGGACGTCTCATCGTACCTGGAGGGCCA GGCGGCGCAGGAGTTCATCGCGTGGCTGGTGGACGGCCGCGGC 18 CATGGAGAGGGAACTTTCACATCTGATGTGAGCTCTTACCTGGAAGGACAG GCCGCCCAGGAGTTTATCGCCTGGCTGGTGGACGGCAGAGGC 19 CATGGGGAGGGAACTTTTACTTCTGATGTTAGCTCCTACCTGGAAGGACAG GCTGCTCAAGAATTTATTGCTTGGCTGGTGGATGGAAGGGGC 20 CACGGCGAAGGCACCTTTACCAGCGATGTGAGCAGCTACCTGGAAGGCCA GGCCGCCCAGGAATTTATTGCCTGGCTGGTGGATGGCAGGGGC 21 CATGGAGAGGGAACTTTTACTTCAGATGTGTCATCATACCTGGAGGGCCAG GCAGCACAGGAGTTTATTGCATGGCTGGTGGATGGCAGAGGC 22 CATGGAGAGGGAACTTTCACATCTGATGTGAGCTCTTACCTGGAAGGACAG GCTGCCCAGGAGTTTATTGCCTGGCTGGTGGATGGCAGAGGC 23 CATGGGGAGGGAACTTTTACTTCTGATGTTAGCTCCTACCTGGAAGGACAG GCTGCTCAAGAATTTATTGCTTGGCTGGTGGATGGAAGGGGC 24 CATGGAGAAGGCACCTTTACCTCTGATGTGAGCAGCTACCTGGAAGGCCA GGCTGCCCAGGAATTTATTGCCTGGCTGGTGGATGGCAGGGGC 25 TACGGCGAGGGCACGTTCACGTCGGACTACTCGATCGGCCTGGACAAGAT CGCGCAGAAGAAGGCGTTCGTGCAGTGGCTGATCGCGGGCGGCCCGTCGTCG GGCGCGCCGCCGCCGTCG 26 TACGGCGAGGGCACATTCACCAGCGACTATTCCATTGGACTGGACAAGATT GCTCAGAAGAAGGCCTTTGTGCAGTGGCTGATCGCCGGCGGACCTTCTAGCGG CGCCCCTCCTCCTAGC 27 TATGGGGAAGGGACTTTCACTTCAGACTACTCCATTGGTCTTGATAAAATCG CTCAAAAGAAGGCTTTCGTGCAGTGGCTCATCGCCGGTGGCCCCTCATCCGGC GCACCCCCTCCGAGC 28 TACGGCGAGGGCACCTTCACCAGCGATTACAGCATTGGCCTGGACAAAATC GCCCAGAAAAAAGCCTTTGTGCAGTGGCTGATTGCCGGCGGCCCCAGCAGCG GAGCCCCCCCCCCCAGC 29 TATGGCGAGGGAACGTTTACGTCGGACTATTCAATTGGCCTGGACAAGATT GCGCAGAAGAAGGCGTTCGTGCAGTGGCTGATCGCGGGCGGCCCGTCGTCGG GCGCGCCGCCGCCGTCG 30 TATGGCGAGGGAACTTTCACCAGCGACTATTCTATTGGACTGGACAAGATT GCTCAGAAGAAGGCCTTTGTCCAGTGGCTGATCGCCGGCGGACCTTCTAGCGG CGCCCCTCCTCCTAGC 31 TATGGGGAAGGGACTTTCACTTCAGACTACTCTATTGGTCTTGATAAAATCG CTCAAAAGAAGGCGTTCGTGCAGTGGCTCATCGCCGGTGGCCCCTCGTCCGGC GCACCCCCACCGAGC 32 TATGGCGAGGGCACCTTCACCAGCGATTATTCTATTGGCCTGGACAAAATCG CCCAGAAAAAAGCCTTTGTCCAGTGGCTGATTGCCGGCGGCCCCAGCAGCGG AGCCCCCCCCCCCAGC 33 TATGGAGAGGGAACTTTTACTTCAGACTATTCAATTGGCCTGGACAAGATT GCTCAGAAGAAGGCTTTTGTCCAGTGGCTGATTGCAGGAGGCCCAAGTTCAG GAGCACCACCACCATCA 34 TATGGAGAGGGAACTTTCACCTCTGACTATTCTATTGGACTGGACAAGATTG CTCAGAAGAAGGCCTTTGTCCAGTGGCTGATTGCAGGAGGACCTTCTTCTGGA GCCCCTCCTCCTAGC 35 TATGGGGAAGGGACTTTCACTTCAGACTACTCTATTGGTCTTGATAAAATTG CTCAAAAGAAGGCTTTTGTCCAGTGGTTGATTGCTGGTGGCCCCTCCTCTGGA GCACCCCCACCAAGC 36 TATGGAGAGGGCACCTTCACCTCTGATTATTCTATTGGCCTGGACAAAATTG CCCAGAAAAAAGCCTTTGTCCAGTGGCTGATTGCTGGAGGCCCCAGCTCTGG AGCCCCCCCCCCCAGC 37 ATGGTGGCGACGAAGACGTTCGCGCTGCTGCTGCTGTCGCTGTTCCTGGCG GTGGGCCTGGGCGAGAAGAAGGAGGGCCACTTCTCGGCGCTGCCGTCGCTGC CGGTGGGCTCGCACGCGAAGGTGTCGTCGCCGCAGCCGCGCGGCCCGCGCTA CGCGGAGGGCACGTTCATCTCGGACTACTCGATCGCGATGGACAAGATCCACC AGCAGGACTTCGTGAACTGGCTGCTGGCGCAGAAGGGCAAGAAGAACGACT GGAAGCACAACATCACGCAGCGCGAGGCGCGCGCGCTGGAGCTGGCGTCGCA GGCGAACCGCAAGGAGGAGGAGGCGGTGGAGCCGCAGTCGTCGCCGGCGAA GAACCCGTCGGACGAGGACCTGCTGCGCGACCTGCTGATCCAGGAGCTGCTG GCGTGCCTGCTGGACCAGACGAACCTGTGCCGCCTGCGCTCGCGC 38 ATGGTGGCCACAAAGACCTTCGCCCTGCTGCTGCTGAGCCTGTTTCTGGCC GTGGGCCTGGGCGAGAAGAAGGAAGGGCATTTTTCCGCCCTGCCAAGCCTGC CTGTGGGCTCCCACGCCAAGGTGAGCTCCCCACAGCCTAGAGGCCCCCGCTAT GCAGAGGGCACTTTCATTTCCGATTATAGCATCGCCATGGATAAAATCCATCAG CAGGACTTCGTGAACTGGCTGCTGGCTCAGAAGGGGAAAAAGAACGACTGG AAGCACAATATCACCCAGAGAGAGGCCAGAGCCCTGGAGCTGGCCTCTCAGG CCAATCGGAAGGAAGAGGAAGCTGTGGAGCCCCAGTCTTCCCCTGCCAAGAA CCCCAGCGATGAGGACCTGCTGCGAGACCTGCTGATCCAGGAACTGCTGGCCT GCCTCCTGGACCAGACCAACCTGTGCAGACTGCGGTCCCGG 39 ATGGTGGCAACTAAGACTTTTGCACTGCTTTTGCTGTCTCTCTTCTTGGCTG TGGGACTGGGAGAAAAGAAGGAGGGCCACTTCAGCGCCCTGCCATCTCTTCC TGTCGGAAGCCATGCTAAAGTGTCTAGTCCTCAGCCCCGCGGGCCTAGATACG CCGAAGGAACCTTTATCAGCGACTACAGTATCGCTATGGACAAAATTCACCAG CAGGACTTCGTTAATTGGCTCCTGGCGCAGAAGGGGAAGAAAAACGATTGGA AACACAACATCACCCAGAGGGAGGCGCGAGCCCTGGAGCTGGCCTCTCAAGC CAATCGCAAGGAGGAGGAAGCCGTGGAGCCTCAGTCCTCTCCTGCAAAAAAT CCCAGCGATGAGGACCTGCTCCGGGACCTCCTGATTCAGGAACTGCTCGCTTG CCTGCTGGACCAGACCAATTTGTGTAGACTCAGGTCTCGG 40 ATGGTGGCCACCAAGACCTTTGCCCTGCTGCTGCTGAGCCTGTTCCTGGCA GTGGGCCTCGGCGAGAAGAAAGAGGGTCACTTCAGCGCCCTCCCCAGCCTGC CCGTTGGCTCTCATGCCAAGGTGAGCAGCCCCCAGCCCAGGGGCCCCAGGTA CGCCGAAGGCACTTTCATCAGCGACTACAGCATCGCCATGGACAAGATCCACC AGCAGGACTTTGTGAACTGGCTGCTGGCCCAGAAGGGCAAGAAGAATGACTG GAAACACAACATCACCCAGAGGGAGGCCAGGGCCCTGGAGCTGGCCAGCCA GGCCAATAGGAAGGAGGAGGAGGCAGTGGAGCCACAGAGCAGCCCAGCCAA GAACCCCAGCGATGAAGATCTGCTGAGGGACCTGCTGATCCAGGAGCTGCTG GCCTGCCTGCTGGATCAGACAAACCTCTGCAGGCTCAGGTCTAGG 41 ATGGTGGCGACGAAGACGTTTGCGCTGCTGCTGCTGTCGCTGTTCCTGGCG GTGGGCCTGGGCGAGAAGAAGGAGGGCCACTTCTCAGCGCTGCCGTCGCTGC CGGTGGGCTCGCACGCGAAGGTGTCGTCGCCGCAGCCGCGCGGCCCGCGGTA CGCGGAGGGAACGTTCATCTCGGACTATTCAATTGCGATGGACAAGATCCACC AGCAGGACTTTGTCAACTGGCTGCTGGCGCAGAAGGGCAAGAAGAACGATTG GAAGCATAACATAACGCAGAGAGAGGCGCGGGCGCTGGAGCTGGCGTCGCAG GCGAACCGCAAGGAGGAGGAGGCGGTGGAGCCGCAGTCGTCGCCGGCGAAG AACCCGTCGGACGAGGACCTGCTCCGCGACCTGCTGATCCAGGAGCTGCTCG CGTGCCTGCTGGACCAGACGAACCTGTGCCGCCTGCGCTCGCGC 42 ATGGTGGCAACAAAGACCTTCGCCCTGCTGCTGCTGAGCCTGTTTCTGGCA GTGGGCCTGGGCGAGAAGAAGGAAGGGCACTTTAGCGCCCTGCCAAGCCTGC CTGTGGGCTCCCATGCCAAGGTGAGCTCCCCTCAGCCTAGAGGCCCTCGCTAT GCAGAGGGAACTTTTATTAGCGATTATAGCATCGCCATGGATAAAATCCATCAG CAGGACTTTGTCAACTGGCTGCTGGCTCAGAAGGGGAAAAAGAACGATTGGA AGCATAATATCACCCAGAGAGAGGCCAGAGCCCTGGAGCTGGCCTCTCAGGCC AATCGCAAGGAAGAGGAAGCAGTGGAGCCCCAGTCTTCCCCTGCCAAGAACC CCAGCGATGAGGACCTGCTGCGAGACCTGCTGATCCAGGAACTGCTGGCCTG CCTCCTGGACCAGACCAACCTGTGCAGACTGCGGTCCCGG 43 ATGGTGGCAACTAAGACTTTTGCACTGCTTTTGCTGTCTCTCTTCCTTGCAG TGGGACTTGGAGAAAAGAAGGAGGGCCACTTCAGCGCCCTGCCATCTCTTCC TGTAGGAAGCCATGCTAAAGTGTCTAGTCCTCAGCCTCGCGGGCCTAGATACG CTGAAGGAACCTTTATCAGCGACTATAGTATCGCTATGGACAAAATTCACCAGC AGGACTTCGTTAATTGGCTCCTGGCGCAGAAGGGGAAGAAAAACGATTGGAA ACATAACATCACCCAGAGGGAGGCGCGAGCCCTGGAGCTGGCCTCTCAAGCC AATCGCAAGGAGGAGGAAGCAGTGGAGCCTCAGTCCTCTCCTGCAAAAAATC CCAGCGATGAGGACCTGCTCCGCGACCTCCTGATTCAGGAACTGCTCGCTTGC CTGCTGGACCAGACCAACTTGTGTAGACTCAGGTCTCGG 44 ATGGTGGCCACCAAGACCTTTGCCCTGCTGCTGCTGAGCCTGTTCCTGGCA GTGGGGCTCGGCGAGAAGAAAGAGGGTCACTTCAGCGCCCTCCCCAGCCTAC CTGTTGGCTCTCATGCCAAGGTGAGCAGCCCCCAGCCCAGGGGCCCCAGGTAC GCTGAAGGCACTTTCATCAGCGACTATAGCATCGCCATGGACAAGATCCACCA GCAGGACTTTGTCAACTGGCTGCTGGCCCAGAAGGGCAAGAAGAACGATTGG AAACATAACATCACCCAGAGGGAGGCCAGGGCCCTGGAGCTGGCCAGCCAGG CCAATAGGAAGGAGGAGGAGGCAGTGGAGCCTCAGAGCAGCCCAGCCAAGA ACCCCAGCGATGAAGATCTGCTGAGGGACCTGCTGATCCAGGAGCTGCTGGCC TGCCTGCTGGATCAGACAAACCTCTGCAGGCTCAGGTCTAGG 45 ATGGTGGCAACTAAGACTTTTGCACTGCTGCTGCTGTCACTGTTCCTGGCA GTGGGCCTGGGGGAGAAGAAGGAGGGCCACTTCTCAGCACTGCCATCACTGC CAGTGGGCTCACATGCAAAGGTGTCATCACCTCAGCCTAGAGGCCCAAGATAT GCAGAGGGAACTTTCATCTCAGACTATTCAATTGCTATGGACAAGATCCACCA GCAGGACTTTGTCAACTGGCTGCTGGCTCAGAAGGGCAAGAAGAATGACTGG AAGCATAATATTACTCAGAGAGAGGCAAGAGCACTGGAGCTGGCATCACAGGC AAACAGAAAGGAGGAGGAGGCAGTGGAGCCTCAGTCATCACCAGCAAAGAA CCCATCAGATGAGGACCTGCTCAGAGACCTGCTGATCCAGGAGCTGCTGGCAT GCCTGCTGGACCAGACTAACCTGTGCAGACTGAGATCAAGA 46 ATGGTGGCAACAAAGACCTTTGCCCTGCTGCTGCTGAGCCTGTTTCTGGCT GTTGGCCTGGGGGAGAAGAAGGAAGGGCACTTTTCTGCCCTGCCAAGCCTGC CTGTGGGCTCCCATGCCAAGGTGAGCTCCCCTCAGCCTAGAGGCCCTAGATAT GCAGAGGGAACTTTTATTTCTGATTATTCTATTGCCATGGATAAAATCCATCAGC AGGACTTTGTCAACTGGCTGCTGGCTCAGAAGGGGAAAAAGAATGACTGGAA GCATAATATCACCCAGAGAGAGGCCAGAGCCCTGGAGCTGGCCTCTCAGGCCA ATAGAAAGGAAGAGGAAGCAGTGGAGCCCCAGTCTTCCCCTGCCAAGAACCC CTCTGATGAGGACCTGCTGAGAGACCTGCTGATCCAGGAACTGCTGGCCTGCC TCCTGGACCAGACCAACCTGTGCAGACTGAGATCCAGA 47 ATGGTGGCAACTAAGACTTTTGCACTGCTTTTGCTGTCTCTCTTCCTTGCAG TGGGACTTGGAGAAAAGAAGGAGGGCCACTTCTCTGCCCTGCCATCTCTACCT GTTGGAAGCCATGCTAAAGTGTCTAGTCCTCAGCCTAGAGGGCCTAGATATGCT GAAGGAACCTTTATCTCTGACTATAGTATTGCTATGGACAAAATTCACCAGCAG GACTTTGTTAATTGGCTCCTGGCTCAGAAGGGGAAGAAAAATGATTGGAAACA TAACATCACCCAGAGGGAGGCAAGAGCCCTGGAGCTGGCCTCTCAAGCCAAT AGAAAGGAGGAGGAAGCTGTTGAGCCTCAGTCCTCTCCTGCAAAAAATCCCT CTGATGAGGACCTGCTCAGAGACCTCCTGATTCAGGAACTGTTGGCTTGCCTG CTGGACCAGACCAACTTGTGTAGACTCAGGTCTAGA 48 ATGGTGGCCACCAAGACCTTTGCCCTGCTGCTGCTGAGCCTGTTCCTGGCA GTGGGGTTGGGGGAGAAGAAAGAGGGTCACTTCTCTGCCCTCCCCAGCCTAC CTGTTGGCTCTCATGCCAAGGTGAGCAGCCCCCAGCCCAGGGGCCCCAGGTAT GCTGAAGGCACTTTCATCTCTGACTATTCTATTGCCATGGACAAGATCCACCAG CAGGACTTTGTCAACTGGCTGCTGGCCCAGAAGGGCAAGAAGAATGACTGGA AACATAACATCACCCAGAGGGAGGCCAGGGCCCTGGAGCTGGCCAGCCAGGC CAATAGGAAGGAGGAGGAGGCAGTGGAGCCTCAGAGCAGCCCAGCCAAGAA CCCCTCTGATGAAGATCTGCTGAGGGACCTGCTGATCCAGGAGCTGCTGGCCT GCCTGCTGGATCAGACAAACCTCTGCAGGCTCAGGTCTAGG 49 ATGAAGTCGATCTACTTCGTGGCGGGCCTGTTCGTGATGCTGGTGCAGGGC TCGTGGCAGCGCTCGCTGCAGGACACGGAGGAGAAGTCGCGCTCGTTCTCGG CGTCGCAGGCGGACCCGCTGTCGGACCCGGACCAGATGAACGAGGACAAGCG CCACTCGCAGGGCACGTTCACGTCGGACTACTCGAAGTACCTGGACTCGCGCC GCGCGCAGGACTTCGTGCAGTGGCTGATGAACACGAAGCGCAACCGCAACAA CATCGCGAAGCGCCACGACGAGTTCGAGCGCCACGCGGAGGGCACGTTCACG TCGGACGTGTCGTCGTACCTGGAGGGCCAGGCGGCGAAGGAGTTCATCGCGT GGCTGGTGAAGGGCCGCGGCCGCCGCGACTTCCCGGAGGAGGTGGCGATCGT GGAGGAGCTGGGCCGCCGCCACGCGGACGGCTCGTTCTCGGACGAGATGAAC ACGATCCTGGACAACCTGGCGGCGCGCGACTTCATCAACTGGCTGATCCAGAC GAAGATCACGGACCGCAAG 50 ATGAAGAGCATCTACTTCGTGGCCGGCCTGTTCGTGATGCTGGTGCAGGGC TCTTGGCAGCGCTCCCTGCAGGATACCGAGGAGAAGAGCCGGAGCTTTTCCGC CAGCCAGGCCGACCCTCTGAGCGACCCAGATCAGATGAACGAGGATAAACGG CACAGCCAGGGCACTTTCACATCCGACTACTCTAAGTACCTGGATAGCCGGCG CGCACAAGATTTTGTGCAGTGGCTGATGAATACTAAGCGGAATAGGAACAACA TCGCCAAACGCCACGACGAGTTCGAGAGGCACGCCGAAGGCACCTTCACCTC CGACGTGAGCAGCTACCTGGAGGGACAGGCCGCCAAGGAGTTCATCGCCTGG CTGGTGAAGGGCCGGGGCCGGCGGGACTTTCCTGAGGAAGTGGCCATCGTGG AGGAACTGGGCAGAAGGCACGCCGACGGGAGCTTCTCAGACGAGATGAACA CTATTCTGGACAATCTGGCTGCCCGGGACTTCATCAATTGGCTGATCCAGACCA AAATCACCGACAGGAAG 51 ATGAAGAGCATCTACTTCGTCGCCGGTCTTTTTGTGATGCTCGTGCAAGGCT CCTGGCAACGCAGCCTGCAAGATACAGAGGAAAAATCCAGATCATTCTCCGCA TCCCAGGCCGACCCCTTGTCTGACCCCGATCAGATGAATGAAGATAAGAGGCA CTCACAGGGGACCTTCACTAGCGATTATTCCAAATATCTGGATTCACGCAGAGC ACAGGACTTCGTGCAGTGGCTTATGAATACAAAAAGAAACCGAAACAATATTG CGAAGCGCCACGACGAGTTTGAGCGACATGCAGAGGGCACCTTTACTAGCGA CGTATCTTCCTACCTGGAGGGCCAGGCCGCCAAGGAGTTTATAGCCTGGCTTGT TAAGGGTCGCGGCAGGCGCGATTTCCCCGAGGAAGTGGCCATCGTGGAAGAG CTGGGACGCAGACACGCGGACGGCTCTTTCTCCGATGAAATGAACACAATACT TGACAATCTGGCTGCTCGCGACTTTATTAATTGGCTCATCCAGACTAAGATCAC TGATCGAAAA 52 ATGAAGAGCATCTACTTCGTGGCCGGGCTGTTCGTGATGCTGGTGCAGGGC AGCTGGCAGCGGAGCCTGCAGGACACAGAGGAGAAGAGCAGAAGCTTCAGC GCCAGCCAGGCAGACCCCCTCAGCGACCCCGACCAGATGAACGAGGACAAG AGGCACAGCCAGGGCACATTCACCAGCGACTACAGCAAGTACCTGGACAGCA GGAGGGCCCAGGACTTCGTGCAGTGGCTGATGAATACCAAGAGGAACAGGAA TAACATCGCCAAGAGGCACGACGAGTTCGAGAGACACGCCGAGGGGACCTTC ACCAGCGATGTGAGCTCTTACCTGGAGGGCCAGGCCGCCAAGGAGTTCATCGC CTGGCTGGTGAAGGGCAGGGGAAGGAGGGACTTCCCCGAGGAGGTCGCCATC GTTGAGGAGCTGGGCAGAAGACACGCCGACGGTTCTTTCTCTGACGAGATGA ACACCATCCTGGACAATCTGGCCGCCAGGGACTTCATAAACTGGCTGATCCAG ACCAAGATCACTGACAGGAAG 53 ATGAAATCGATCTACTTTGTCGCGGGCCTGTTCGTGATGCTGGTGCAGGGTT CGTGGCAGCGCTCGCTGCAGGACACGGAGGAGAAGTCGCGATCGTTCTCAGC ATCGCAGGCAGACCCGCTGTCGGACCCGGACCAGATGAACGAAGACAAGCGC CACTCGCAGGGAACGTTTACGTCGGACTATTCGAAGTACCTGGACTCGCGCCG GGCGCAGGACTTTGTCCAGTGGCTGATGAACACGAAGCGCAACCGCAACAAT ATTGCGAAGCGGCACGACGAGTTTGAGCGGCACGCGGAGGGAACGTTTACGT CGGACGTCTCATCGTACCTGGAGGGCCAGGCGGCGAAGGAGTTCATCGCGTG GCTGGTGAAGGGCCGCGGCCGCCGCGACTTTCCGGAGGAGGTGGCGATAGTG GAGGAGCTGGGCCGCCGGCACGCGGACGGTTCGTTCTCGGACGAGATGAACA CTATCCTGGACAACCTGGCGGCGCGCGACTTCATCAACTGGCTGATCCAGACG AAGATCACGGACCGCAAG 54 ATGAAGAGCATCTACTTTGTCGCCGGCCTGTTCGTGATGCTGGTGCAGGGC TCTTGGCAGCGCTCCCTGCAGGATACTGAGGAGAAGTCACGGAGCTTTAGCGC CAGCCAGGCCGACCCTCTGAGCGACCCAGATCAGATGAACGAAGATAAGCGG CATAGCCAGGGCACTTTCACTAGCGACTACTCTAAGTACCTGGATAGCCGGCG CGCACAAGATTTTGTCCAGTGGCTGATGAATACTAAGCGCAATAGGAACAACA TCGCCAAAAGGCACGACGAGTTTGAGAGGCACGCGGAAGGCACCTTCACCAG CGATGTGAGCAGCTACCTGGAGGGACAGGCCGCCAAGGAGTTCATCGCCTGG CTGGTGAAGGGCCGCGGCCGGCGGGACTTTCCTGAGGAAGTGGCGATAGTGG AGGAACTGGGCAGAAGGCACGCCGACGGGAGCTTCTCAGACGAGATGAACA CTATTCTGGACAATCTGGCTGCACGGGACTTCATCAATTGGCTGATCCAGACCA AAATCACCGACAGGAAG 55 ATGAAGAGCATCTACTTCGTCGCCGGTCTTTTTGTCATGCTCGTGCAAGGCT CCTGGCAACGCAGCCTGCAAGATACTGAGGAAAAATCCAGAAGTTTCTCCGC ATCCCAGGCCGACCCCTTGTCTGACCCTGATCAGATGAACGAAGATAAGAGGC ACTCACAGGGGACCTTCACTAGCGATTATTCCAAATATCTGGATAGTCGCAGAG CACAGGACTTTGTCCAGTGGCTTATGAATACTAAAAGGAACCGCAACAATATT GCGAAGCGGCACGACGAGTTTGAGCGACATGCAGAGGGCACCTTTACTAGCG ACGTATCTTCCTACCTGGAGGGCCAGGCCGCCAAGGAGTTTATAGCCTGGCTT GTTAAGGGGCGCGGCAGACGCGATTTCCCTGAGGAAGTGGCGATAGTGGAAG AGCTGGGACGCAGACACGCGGACGGCTCTTTCAGCGATGAGATGAACACTATA CTTGACAATCTGGCTGCTCGCGACTTTATTAATTGGCTCATCCAGACTAAGATC ACTGATCGCAAA 56 ATGAAGAGCATCTACTTTGTCGCCGGGCTGTTCGTGATGCTGGTGCAGGGC AGCTGGCAGCGGAGCCTGCAGGACACTGAGGAGAAGAGCAGAAGCTTCAGC GCCAGCCAGGCAGACCCCCTCAGCGACCCTGACCAGATGAACGAAGACAAGA GGCATAGCCAGGGAACTTTCACCAGCGACTATAGCAAGTACCTGGACAGCAGG AGGGCCCAGGACTTTGTCCAGTGGCTGATGAATACCAAGAGGAATAGGAATAA CATCGCCAAGAGGCACGACGAGTTTGAGAGACACGCTGAGGGGACCTTCACC AGCGATGTGAGCTCTTACCTGGAGGGCCAGGCCGCCAAGGAGTTCATCGCCTG GCTGGTGAAGGGCAGGGGAAGGAGGGACTTCCCTGAGGAGGTCGCCATCGTT GAGGAGCTGGGCAGAAGACACGCCGACGGTTCTTTCTCTGACGAGATGAACA CCATCCTGGACAATCTGGCCGCCAGGGACTTCATAAACTGGCTGATCCAGACC AAGATCACTGACAGGAAG 57 ATGAAATCAATCTACTTTGTTGCAGGCCTGTTTGTCATGCTGGTGCAGGGTT CATGGCAGAGATCACTGCAGGACACTGAGGAGAAGTCAAGAAGTTTCTCAGC ATCACAGGCAGACCCACTGTCAGACCCAGACCAGATGAATGAGGACAAGAGA CACTCACAGGGAACTTTTACTTCAGACTATTCAAAGTACCTGGACAGTAGAAG AGCACAGGACTTTGTCCAGTGGCTGATGAACACTAAGAGAAACAGAAACAAT ATTGCAAAGAGACATGATGAGTTTGAGAGACATGCAGAGGGAACTTTTACTTC AGATGTGTCATCATACCTGGAGGGCCAGGCAGCAAAGGAGTTTATTGCATGGC TGGTGAAGGGCAGAGGCAGAAGAGACTTTCCAGAGGAGGTGGCAATTGTTGA GGAGCTGGGCAGAAGACATGCAGATGGAAGTTTCTCAGATGAGATGAACACT ATCCTGGACAACCTGGCAGCAAGAGACTTCATCAACTGGCTGATCCAGACTAA GATCACTGACAGAAAG 58 ATGAAGAGCATCTACTTTGTTGCTGGCCTGTTTGTCATGCTGGTGCAGGGCT CTTGGCAGAGATCCCTGCAGGATACTGAGGAGAAGTCAAGAAGCTTTTCTGCC AGCCAGGCTGACCCTCTGTCTGACCCAGATCAGATGAATGAGGATAAGAGACA TAGCCAGGGCACTTTCACTTCTGACTACTCTAAGTACCTGGATAGCAGAAGAG CACAAGATTTTGTCCAGTGGCTGATGAATACTAAGAGAAATAGGAACAATATTG CCAAAAGACATGATGAGTTTGAGAGGCATGCTGAAGGCACCTTCACCTCTGAT GTGAGCAGCTACCTGGAGGGACAGGCTGCCAAGGAGTTTATTGCCTGGCTGGT GAAGGGCAGAGGCAGAAGAGACTTTCCTGAGGAAGTGGCTATTGTTGAGGAA CTGGGCAGAAGGCATGCAGATGGGAGCTTCTCAGATGAGATGAACACTATTCT GGACAATCTGGCTGCAAGAGACTTCATCAATTGGCTGATCCAGACCAAAATCA CTGACAGGAAG 59 ATGAAGAGCATCTACTTTGTTGCTGGTCTTTTTGTCATGTTGGTGCAAGGCT CCTGGCAAAGAAGCCTGCAAGATACTGAGGAAAAATCCAGAAGTTTCTCTGC ATCCCAGGCTGACCCCTTGTCTGACCCTGATCAGATGAATGAAGATAAGAGGC ACTCACAGGGGACCTTCACTTCTGATTATTCCAAATATCTGGATAGTAGAAGAG CACAGGACTTTGTCCAGTGGCTTATGAATACTAAAAGGAACAGAAACAATATT GCAAAGAGACATGATGAGTTTGAGAGACATGCAGAGGGCACCTTTACTTCAG ATGTATCTTCCTACCTGGAGGGCCAGGCTGCCAAGGAGTTTATAGCCTGGCTTG TTAAGGGGAGAGGCAGAAGAGATTTCCCTGAGGAAGTGGCTATTGTTGAAGA GCTGGGACGCAGACATGCAGATGGCTCTTTCTCTGATGAGATGAACACTATACT TGACAATCTGGCTGCAAGAGACTTTATTAATTGGCTCATCCAGACTAAGATCAC TGATAGAAAA 60 ATGAAGAGCATCTACTTTGTTGCTGGGCTGTTTGTCATGCTGGTGCAGGGC AGCTGGCAGAGAAGCCTGCAGGACACTGAGGAGAAGAGCAGAAGCTTCTCT GCCAGCCAGGCAGACCCCCTCTCTGACCCTGACCAGATGAATGAGGACAAGA GGCATAGCCAGGGAACTTTCACCTCTGACTATAGCAAGTACCTGGACAGCAGG AGGGCCCAGGACTTTGTCCAGTGGCTGATGAATACCAAGAGGAATAGGAATAA TATTGCCAAGAGGCATGATGAGTTTGAGAGACATGCTGAGGGGACCTTCACCT CTGATGTGAGCTCTTACCTGGAGGGCCAGGCTGCCAAGGAGTTTATTGCCTGG CTGGTGAAGGGCAGGGGAAGGAGGGACTTCCCTGAGGAGGTTGCTATTGTTG AGGAGCTGGGCAGAAGACATGCTGATGGTTCTTTCTCTGATGAGATGAACACC ATCCTGGACAATCTGGCTGCCAGGGACTTCATAAACTGGCTGATCCAGACCAA GATCACTGACAGGAAG 61 TACGGCCAGGGCACGTTCACGTCGGACTACTCGATCATCCTGGACAAGAA GGCGCAGGCGGCGTTCATCGAGTACCTGCTGGAGGGCGGCCCGTCGTCGGGC GCGCCGCCGCCGTCG 62 TACGGCCAGGGCACCTTTACCTCTGACTACTCTATTATTCTGGATAAGAAAG CCCAGGCCGCCTTCATCGAGTACCTGCTGGAGGGAGGCCCATCTTCCGGCGCC CCCCCACCCAGC 63 TATGGTCAAGGGACATTCACGTCCGACTACAGTATTATTCTTGACAAGAAG GCTCAAGCCGCGTTTATTGAGTATTTGTTGGAGGGAGGTCCAAGCAGTGGAGC CCCCCCTCCTAGC 64 TATGGCCAGGGCACCTTCACCAGCGACTACAGCATCATTCTGGACAAAAAA GCCCAGGCCGCCTTTATTGAGTATCTGCTGGAGGGCGGCCCCAGCAGCGGCGC CCCCCCCCCCAGC 65 TATGGCCAGGGAACGTTTACGTCGGACTATTCAATCATCCTGGACAAGAAG GCGCAGGCGGCGTTTATTGAGTACCTGCTGGAGGGCGGCCCGTCGTCGGGCGC GCCGCCGCCGTCG 66 TATGGCCAGGGCACCTTTACCTCTGACTACTCTATTATTCTGGATAAGAAAG CCCAGGCCGCCTTTATTGAGTACCTGCTGGAGGGAGGCCCATCGTCCGGCGCC CCCCCACCCAGC 67 TATGGTCAAGGGACTTTCACTAGCGACTATAGTATTATTCTTGACAAGAAGG CTCAAGCTGCGTTTATTGAGTATTTGTTGGAGGGAGGTCCAAGCAGTGGAGCC CCCCCTCCTAGC 68 TATGGCCAGGGCACCTTCACCAGCGACTATAGCATAATTCTGGACAAAAAA GCCCAGGCCGCCTTTATTGAGTATCTGCTGGAGGGCGGCCCCAGCAGCGGCGC CCCCCCCCCCAGC 69 TATGGCCAGGGAACTTTTACTTCAGACTATTCAATCATCCTGGACAAGAAG GCACAGGCAGCTTTTATTGAGTACCTGCTGGAGGGAGGCCCAAGTTCAGGAG CACCACCACCATCA 70 TATGGCCAGGGCACCTTTACCTCTGACTACTCTATTATTCTGGATAAGAAAG CCCAGGCTGCCTTTATTGAGTACCTGCTGGAGGGAGGCCCATCCTCTGGAGCC CCCCCACCCAGC 71 TATGGTCAAGGGACTTTCACTTCTGACTATAGTATTATTCTTGACAAGAAGG CTCAAGCTGCTTTTATTGAGTATTTGTTGGAGGGAGGTCCAAGCAGTGGAGCC CCCCCTCCTAGC 72 TATGGCCAGGGCACCTTCACCTCTGACTATAGCATAATTCTGGACAAAAAA GCCCAGGCTGCCTTTATTGAGTATCTGCTGGAGGGAGGCCCCAGCTCTGGAGC CCCCCCCCCCAGC 73 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATCGTGCTGTCGGTGGCGCTG AACCACCTGAAGGCGACGCCGATCGAGTCGCACCAGGTGGAGAAGCGCAAGT GCAACACGGCGACGTGCGCGACGCAGCGCCTGGCGAACTTCCTGGTGCACTC GTCGAACAACTTCGGCGCGATCCTGTCGTCGACGAACGTGGGCTCGAACACG TACGGCAAGCGCAACGCGGTGGAGGTGCTGAAGCGCGAGCCGCTGAACTACC TGCCGCTG 74 ATGGGCATCCTGAAGCTGCAGGTGTTTCTGATCGTCCTGAGCGTGGCCCTG AACCATCTGAAGGCCACCCCTATCGAGAGCCACCAGGTGGAGAAGAGAAAAT GCAACACAGCCACCTGTGCCACCCAGCGCCTGGCCAATTTTCTGGTGCACAGC AGCAACAACTTCGGAGCCATCCTGTCTTCCACCAACGTGGGCAGCAACACCTA CGGAAAGAGGAATGCCGTGGAGGTGCTGAAACGGGAACCCCTGAACTATCTG CCCCTG 75 ATGGGAATCCTGAAGCTCCAGGTGTTCCTGATTGTTCTGAGTGTGGCCCTT AACCATTTGAAGGCAACACCCATTGAGAGCCACCAGGTCGAGAAGAGAAAGT GCAATACTGCCACCTGTGCTACTCAGCGCCTGGCCAATTTCCTGGTTCACTCTT CCAATAACTTTGGAGCCATTCTGTCATCCACCAATGTTGGGTCCAACACCTATG GAAAGAGAAACGCAGTTGAGGTCCTCAAACGCGAGCCACTCAATTACCTGCC GCTT 76 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATCGTGCTGAGCGTGGCCCTG AACCACCTGAAAGCTACCCCCATCGAGAGTCACCAGGTGGAGAAGAGGAAAT GCAACACTGCCACCTGCGCCACCCAGAGGCTGGCCAATTTCCTGGTGCACAG CAGCAACAACTTCGGCGCCATCCTGTCAAGCACCAACGTGGGAAGCAATACCT ACGGCAAGAGGAATGCCGTGGAGGTGCTGAAGAGAGAGCCCCTGAATTACCT GCCCCTG 77 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATCGTGCTGTCGGTGGCGCTG AACCACCTGAAGGCAACACCGATTGAGTCGCACCAGGTGGAGAAGCGCAAGT GCAACACTGCGACGTGCGCGACGCAGCGCCTGGCGAACTTCCTGGTGCACTC ATCGAACAACTTTGGCGCGATCCTGTCGTCGACGAACGTCGGTTCGAACACGT ATGGCAAGAGGAACGCGGTGGAGGTGCTGAAGAGAGAGCCACTGAACTACCT GCCGCTG 78 ATGGGCATCCTGAAGCTGCAGGTGTTTCTGATCGTCCTGTCCGTGGCCCTG AACCATCTGAAGGCCACCCCTATTGAGAGCCACCAGGTGGAGAAGAGAAAGT GCAACACTGCCACCTGTGCCACCCAGCGCCTGGCCAATTTTCTGGTGCATAGC AGCAACAACTTCGGAGCCATCCTGTCTTCCACTAACGTCGGCAGCAACACCTA CGGAAAGAGGAACGCAGTGGAGGTGCTGAAGAGAGAACCCCTGAACTATCTG CCCCTG 79 ATGGGAATCCTGAAGCTCCAGGTGTTCCTGATTGTTCTCAGTGTGGCCCTTA ACCACTTGAAGGCAACACCTATTGAGAGCCACCAGGTTGAGAAGAGAAAGTG CAATACTGCCACCTGTGCTACTCAGCGCCTGGCCAATTTCCTGGTTCACTCTTC CAATAACTTTGGAGCTATTCTGTCATCCACCAACGTTGGGTCCAACACCTATGG AAAGAGAAACGCAGTTGAGGTCCTCAAAAGAGAGCCACTCAATTACCTGCCG CTT 80 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATCGTGCTGTCCGTGGCCCTG AACCACCTGAAAGCTACCCCTATTGAGAGTCACCAGGTGGAGAAGAGGAAGT GCAACACTGCCACCTGCGCCACCCAGAGGCTGGCCAATTTCCTGGTGCATAGC AGCAACAACTTTGGCGCCATCCTGTCAAGCACTAACGTTGGAAGCAATACCTA TGGCAAGAGGAACGCAGTGGAGGTGCTGAAGAGAGAGCCCCTGAATTACCTG CCCCTG 81 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATTGTCCTGTCAGTGGCACTG AACCACCTGAAGGCAACTCCAATTGAGTCACACCAGGTGGAGAAGAGAAAGT GCAACACTGCCACTTGTGCAACTCAGAGACTGGCAAACTTCCTGGTGCACTC ATCAAACAACTTTGGAGCAATCCTGTCATCAACTAATGTTGGATCAAACACTTA TGGCAAGAGAAATGCAGTGGAGGTGCTGAAGAGAGAGCCACTGAACTACCTG CCACTG ATGGGCATCCTGAAGCTGCAGGTGTTTCTGATTGTCCTGAGTGTTGCCCTG AACCATCTGAAGGCCACCCCTATTGAGAGCCACCAGGTGGAGAAGAGAAAGT GCAACACTGCCACCTGTGCCACCCAGAGACTGGCCAATTTTCTGGTGCATAGC AGCAACAACTTTGGAGCCATCCTGTCTTCCACTAATGTGGGCAGCAACACCTA TGGAAAGAGGAATGCTGTTGAGGTGCTGAAGAGAGAACCCCTGAACTATCTG CCCCTG 83 ATGGGAATCCTGAAGCTCCAGGTGTTCCTGATTGTTCTCAGTGTGGCCCTTA ACCACTTGAAGGCAACACCTATTGAGAGCCACCAGGTTGAGAAGAGAAAGTG CAATACTGCCACCTGTGCTACTCAGAGACTGGCCAATTTCCTGGTTCACTCTTC CAATAACTTTGGAGCTATTCTGTCATCCACCAATGTTGGGTCCAACACCTATGG AAAGAGAAATGCAGTTGAGGTCCTCAAAAGAGAGCCACTCAATTACCTGCCA CTT 84 ATGGGCATCCTGAAGCTGCAGGTGTTCCTGATTGTCCTGAGTGTTGCCCTG AACCACCTGAAAGCTACCCCTATTGAGAGTCACCAGGTGGAGAAGAGGAAGT GCAACACTGCCACCTGTGCCACCCAGAGGCTGGCCAATTTCCTGGTGCATAGC AGCAACAACTTTGGAGCCATCCTGTCAAGCACTAATGTTGGAAGCAATACCTA TGGCAAGAGGAATGCTGTTGAGGTGCTGAAGAGAGAGCCCCTGAATTACCTG CCCCTG 85 ATGGACTCGGACGAGACGGGCTTCGAGCACTCGGGCCTGTGGGTGTCGGT GCTGGCGGGCCTGCTGCTGGGCGCGTGCCAGGCGCACCCGATCCCGGACTCG TCGCCGCTGCTGCAGTTCGGCGGCCAGGTGCGCCAGCGCTACCTGTACACGGA CGACGCGCAGCAGACGGAGGCGCACCTGGAGATCCGCGAGGACGGCACGGT GGGCGGCGCGGCGGACCAGTCGCCGGAGTCGCTGCTGCAGCTGAAGGCGCTG AAGCCGGGCGTGATCCAGATCCTGGGCGTGAAGACGTCGCGCTTCCTGTGCCA GCGCCCGGACGGCGCGCTGTACGGCTCGCTGCACTTCGACCCGGAGGCGTGC TCGTTCCGCGAGCTGCTGCTGGAGGACGGCTACAACGTGTACCAGTCGGAGG CGCACGGCCTGCCGCTGCACCTGCCGGGCAACAAGTCGCCGCACCGCGACCC GGCGCCGCGCGGCCCGGCGCGCTTCCTGCCGCTGCCGGGCCTGCCGCCGGCG CTGCCGGAGCCGCCGGGCATCCTGGCGCCGCAGCCGCCGGACGTGGGCTCGT CGGACCCGCTGTCGATGGTGGGCCCGTCGCAGGGCCGCTCGCCGTCGTACGCG TCG 86 ATGGACTCTGATGAAACCGGATTTGAGCACAGTGGCCTTTGGGTCTCTGTG CTGGCCGGCCTGTTATTGGGGGCCTGTCAGGCCCACCCAATTCCCGACTCATC ACCCCTGCTGCAGTTTGGGGGCCAGGTGAGACAGAGATACCTGTACACTGAC GACGCCCAGCAGACAGAAGCCCATCTGGAGATCAGAGAGGATGGGACTGTGG GCGGCGCCGCCGATCAGAGCCCCGAGTCACTGCTGCAGCTCAAAGCACTGAA GCCTGGTGTGATCCAGATCCTGGGCGTGAAGACCAGCAGATTTCTGTGCCAGA GGCCTGATGGGGCCCTGTACGGATCTCTGCATTTTGACCCCGAGGCCTGCTCAT TCAGAGAGCTGCTGCTGGAGGATGGCTATAATGTGTACCAGTCTGAAGCCCAC GGTCTGCCACTGCACCTTCCCGGAAACAAGTCCCCTCATAGGGATCCAGCCCC CAGAGGGCCAGCACGGTTCTTGCCCCTGCCTGGACTGCCTCCCGCCCTGCCTG AGCCACCAGGGATCCTTGCTCCCCAACCCCCAGACGTGGGTAGCTCCGATCCC CTGAGTATGGTCGGCCCCTCCCAGGGCAGATCCCCCAGCTATGCATCA 87 ATGGATTCAGACGAGACAGGATTCGAACACAGCGGCCTGTGGGTGAGCGT ACTCGCAGGCCTTTTGCTCGGGGCCTGCCAAGCCCACCCAATCCCCGATAGCT CCCCTCTCCTGCAATTTGGGGGGCAGGTGCGGCAGCGATACCTGTACACCGAT GACGCACAACAGACTGAAGCCCACCTGGAGATCAGGGAGGATGGCACGGTTG GGGGAGCCGCGGATCAGTCCCCCGAGAGCCTGTTGCAGCTGAAGGCACTGAA GCCTGGTGTTATACAAATCCTCGGGGTGAAAACAAGTCGATTCCTTTGTCAAC GGCCAGATGGTGCCTTGTACGGCAGTCTGCACTTCGACCCCGAGGCGTGCTCA TTTCGGGAGCTGTTGTTGGAGGACGGATACAATGTATACCAGTCTGAGGCCCA CGGCCTCCCTCTGCATCTCCCTGGCAACAAGTCACCTCATAGAGATCCCGCCCC GAGGGGCCCCGCAAGATTTCTCCCACTGCCAGGATTGCCACCTGCGCTGCCTG AACCTCCGGGGATCCTGGCACCACAGCCACCGGACGTGGGCTCCAGCGACCC CCTTTCTATGGTAGGCCCTAGTCAGGGACGAAGTCCGTCCTACGCATCC 88 ATGGACTCTGACGAGACCGGCTTCGAGCACTCAGGACTGTGGGTTTCTGT GCTGGCTGGTCTTCTGCTGGGAGCCTGCCAGGCACACCCCATCCCTGACAGCA GTCCTCTGCTGCAATTCGGCGGCCAAGTCAGGCAGAGGTACCTGTACACAGAT GATGCCCAGCAGACAGAAGCCCACCTGGAGATCAGGGAGGATGGCACCGTGG GCGGCGCCGCTGACCAGAGCCCCGAAAGTCTGCTGCAGCTGAAAGCCTTGAA GCCCGGAGTGATTCAAATCTTGGGAGTCAAGACAAGCAGGTTCCTGTGCCAG AGGCCAGATGGCGCCCTGTATGGCAGCCTGCACTTTGACCCCGAGGCCTGCAG CTTCAGGGAGCTGCTTCTTGAGGACGGATACAACGTTTACCAGAGCGAAGCCC ACGGCCTGCCCCTGCACCTGCCAGGCAACAAGAGCCCACACAGGGACCCTGC ACCCAGGGGACCAGCTCGCTTCCTGCCACTGCCAGGCCTGCCCCCCGCACTGC CTGAGCCACCTGGAATCCTGGCGCCCCAGCCCCCCGATGTGGGCAGCAGCGA CCCCCTGAGCATGGTGGGCCCTAGCCAGGGCAGGAGCCCCAGCTACGCTAGC 89 ATGGACTCGGACGAGACTGGGTTTGAGCACTCAGGCCTGTGGGTGTCGGT GCTCGCGGGCCTGCTGCTGGGCGCGTGCCAGGCGCATCCAATCCCGGACTCGT CGCCGCTGCTGCAGTTTGGCGGCCAGGTGCGCCAGCGCTACCTGTACACGGAC GACGCGCAGCAGACTGAGGCGCACCTGGAGATCCGCGAGGACGGCACGGTG GGCGGCGCGGCGGACCAGAGTCCGGAGTCGCTGCTGCAGCTGAAGGCGCTGA AGCCAGGAGTGATCCAGATCCTGGGAGTGAAGACCAGTCGCTTCCTGTGCCA GCGCCCGGACGGTGCCCTGTATGGCTCGCTGCACTTTGATCCGGAGGCATGTT CGTTCCGCGAGCTGCTGCTGGAGGACGGCTATAACGTCTACCAGTCAGAGGCG CACGGCCTGCCGCTGCACCTGCCGGGCAACAAGTCGCCGCACCGCGACCCAG CGCCGCGCGGCCCGGCTCGCTTCCTTCCGCTGCCGGGCCTGCCGCCGGCGCTT CCGGAGCCGCCGGGCATCCTGGCGCCGCAGCCGCCGGACGTCGGCTCGTCGG ACCCGCTGTCTATGGTGGGCCCGTCGCAGGGCCGCTCGCCTTCGTATGCGTCG 90 ATGGACTCTGATGAAACAGGATTTGAGCATAGTGGCCTTTGGGTCTCCGTG CTGGCCGGCCTGTTATTGGGGGCCTGTCAGGCCCACCCAATTCCTGACTCATCA CCCCTGCTGCAGTTTGGGGGCCAGGTGAGACAGAGATACCTGTACACTGACG ACGCCCAGCAGACAGAAGCCCATCTGGAGATCAGAGAGGATGGAACAGTGGG CGGCGCCGCAGATCAGTCGCCTGAGTCACTGCTGCAGCTCAAAGCACTGAAG CCTGGTGTGATCCAGATCCTGGGAGTGAAGACCAGCAGATTCCTGTGCCAGAG GCCTGATGGGGCCCTCTACGGATCTCTGCACTTTGACCCTGAGGCCTGCAGTTT CAGAGAGCTGCTGCTGGAGGATGGCTATAACGTCTACCAGTCTGAAGCGCACG GTCTGCCACTGCACCTTCCTGGAAACAAGTCCCCTCATAGGGATCCAGCCCCC AGAGGGCCAGCACGGTTCTTGCCCCTGCCTGGACTGCCTCCTGCCCTGCCTGA GCCACCAGGGATCCTTGCTCCCCAACCCCCGGACGTCGGTTCGTCCGATCCCC TGAGTATGGTCGGCCCATCCCAGGGCAGATCCCCCAGCTATGCATCA 91 ATGGATTCAGACGAGACAGGATTCGAACATAGCGGCCTGTGGGTCAGCGTA CTCGCAGGCCTTTTGTTGGGGGCCTGCCAAGCCCACCCAATACCTGATAGCTC CCCTCTCCTGCAATTTGGGGGGCAGGTGCGGCAGCGATACCTGTACACCGATG ACGCTCAACAGACTGAAGCCCACCTGGAGATCAGGGAGGATGGCACGGTTGG GGGAGCCGCGGATCAGTCGCCTGAGAGCCTGTTGCAGCTGAAGGCACTGAAG CCTGGTGTTATTCAAATCTTGGGGGTGAAAACAAGTCGCTTCCTTTGTCAACG CCCAGATGGTGCCTTGTATGGCAGTCTGCACTTTGACCCTGAGGCATGCAGTTT CCGCGAGCTGTTGTTGGAAGATGGATATAACGTTTACCAGTCTGAGGCGCACG GCCTCCCTCTGCATCTCCCTGGCAACAAGTCACCTCATAGAGATCCTGCTCCAA GGGGACCTGCAAGATTTTTGCCACTGCCAGGATTGCCACCTGCGCTGCCTGAA CCTCCAGGGATCCTGGCACCTCAGCCACCGGACGTCGGCTCCAGCGACCCCCT TTCTATGGTAGGCCCTAGTCAGGGACGATCACCGTCCTACGCATCC 92 ATGGACTCTGACGAGACCGGCTTTGAGCACTCAGGCCTGTGGGTTTCCGTG CTGGCTGGTCTTCTGCTGGGAGCCTGCCAGGCTCACCCCATCCCTGACAGCAG TCCTCTGCTGCAGTTTGGCGGCCAAGTCAGGCAGAGGTACCTGTACACTGATG ATGCCCAGCAGACAGAAGCCCACCTGGAGATCAGGGAGGATGGCACGGTGGG CGGCGCTGCTGACCAGTCACCTGAAAGTCTGCTGCAGCTGAAAGCCTTGAAG CCTGGAGTGATTCAAATCTTGGGAGTCAAGACAAGCAGGTTCCTGTGCCAGA GGCCAGATGGCGCCCTGTATGGCAGCCTGCACTTTGACCCTGAGGCCTGCAGC TTCAGGGAGCTGCTTCTTGAAGATGGATATAACGTTTACCAGAGCGAAGCGCA CGGCCTGCCCCTGCACCTGCCAGGCAACAAGAGCCCACACAGGGACCCTGCA CCCAGGGGACCAGCTCGCTTCCTGCCACTGCCAGGCCTGCCCCCTGCACTGCC TGAGCCACCTGGAATCCTGGCGCCCCAGCCACCTGATGTGGGCAGCAGCGAC CCCCTGAGCATGGTGGGCCCTAGCCAGGGCAGGAGCCCCAGCTATGCTAGC 93 ATGGACTCAGATGAGACTGGGTTTGAGCACTCAGGCCTGTGGGTGTCAGT GCTGGCAGGCCTGCTGCTGGGAGCATGCCAGGCTCATCCAATCCCAGACTCAT CACCACTGCTGCAGTTTGGAGGCCAGGTGAGACAGAGATACCTGTACACTGAT GATGCTCAGCAGACTGAGGCACACCTGGAGATCAGAGAGGATGGCACTGTTG GAGGAGCAGCAGACCAGTCACCAGAGTCACTGCTGCAGCTGAAGGCACTGA AGCCAGGAGTGATCCAGATCCTGGGAGTGAAGACTAGTAGATTCCTGTGCCAG AGACCAGATGGAGCCCTGTATGGCTCACTGCACTTTGATCCAGAGGCATGTAG TTTCAGAGAGCTGCTGCTGGAGGATGGCTATAATGTGTACCAGTCAGAGGCAC ATGGCCTGCCACTGCACCTGCCAGGCAACAAGTCACCACATAGAGACCCAGC ACCTAGAGGCCCAGCAAGATTCCTTCCACTGCCAGGCCTGCCACCAGCACTTC CAGAGCCACCAGGCATCCTGGCACCTCAGCCACCAGATGTGGGCTCATCAGAC CCACTAAGTATGGTGGGCCCATCACAGGGCAGATCACCATCATATGCATCA 94 ATGGACTCTGATGAAACAGGATTTGAGCATAGTGGCCTTTGGGTCAGTGTG CTGGCTGGCCTGTTATTGGGGGCCTGTCAGGCCCACCCAATTCCTGACTCATCA CCCCTGCTGCAGTTTGGGGGCCAGGTGAGACAGAGATACCTGTACACTGATGA TGCCCAGCAGACAGAAGCCCATCTGGAGATCAGAGAGGATGGAACAGTTGGA GGAGCTGCTGATCAGAGCCCTGAGTCACTGCTGCAGCTCAAAGCACTGAAGC CTGGTGTGATCCAGATCCTGGGAGTGAAGACCAGCAGATTCCTGTGCCAGAGG CCTGATGGGGCCCTCTATGGATCTCTGCACTTTGACCCTGAGGCCTGCAGTTTC AGAGAGCTGCTGCTGGAGGATGGCTATAATGTGTACCAGTCTGAAGCCCATGG TCTGCCACTGCACCTTCCTGGAAACAAGTCCCCTCATAGGGATCCAGCCCCCA GAGGGCCAGCAAGATTCTTGCCCCTGCCTGGACTGCCTCCTGCCCTGCCTGAG CCACCAGGGATCCTTGCTCCCCAACCCCCAGATGTGGGTAGCTCTGATCCCCT GAGTATGGTTGGCCCATCCCAGGGCAGATCCCCCAGCTATGCATCA 95 ATGGATTCAGATGAGACAGGATTTGAACACTCTGGCCTGTGGGTCTCTGTT TTGGCAGGCCTTTTGTTGGGGGCCTGCCAAGCCCACCCAATACCTGATAGCTC CCCTCTCCTGCAATTTGGGGGGCAGGTGAGACAGAGATACCTGTACACTGATG ATGCTCAACAGACTGAAGCCCACCTGGAGATCAGGGAGGATGGCACTGTTGG GGGAGCTGCAGATCAGTCCCCTGAGAGCCTGTTGCAGCTGAAGGCACTGAAG CCTGGTGTTATTCAAATCTTGGGGGTGAAAACAAGTAGATTCCTTTGTCAAAG ACCAGATGGTGCCTTGTATGGCAGTCTGCACTTTGACCCTGAGGCATGCAGTTT CAGAGAGCTGTTGTTGGAAGATGGATATAATGTATACCAGTCTGAGGCCCATGG CCTCCCTCTGCATCTCCCTGGCAACAAGTCACCTCATAGAGATCCTGCTCCAAG GGGACCTGCAAGATTTTTGCCACTGCCAGGATTGCCACCTGCACTGCCTGAAC CTCCAGGGATCCTGGCACCTCAGCCACCAGATGTGGGCTCCTCTGACCCCCTT TCTATGGTAGGCCCTAGTCAGGGAAGATCACCATCCTATGCATCC 96 ATGGACTCTGATGAGACAGGGTTTGAGCACTCAGGCCTGTGGGTTAGTGTG CTGGCTGGTCTTCTGCTGGGAGCCTGCCAGGCTCACCCCATCCCTGACAGCAG TCCTCTGCTGCAGTTTGGAGGCCAAGTCAGGCAGAGGTACCTGTACACTGATG ATGCCCAGCAGACAGAAGCCCACCTGGAGATCAGGGAGGATGGAACAGTTGG AGGAGCTGCTGACCAGTCACCTGAAAGTCTGCTGCAGCTGAAAGCCTTGAAG CCTGGAGTGATTCAAATCTTGGGAGTCAAGACAAGCAGGTTCCTGTGCCAGA GGCCAGATGGAGCCCTGTATGGCAGCCTGCACTTTGACCCTGAGGCCTGCAGC TTCAGGGAGCTGCTTCTTGAAGATGGATATAATGTTTACCAGTCTGAAGCCCAT GGCCTGCCCCTGCACCTGCCAGGCAACAAGAGCCCACACAGGGACCCTGCAC CCAGGGGACCAGCTAGATTCCTGCCACTGCCAGGCCTGCCCCCTGCACTGCCT GAGCCACCTGGAATCCTGGCACCCCAGCCACCTGATGTGGGCAGCTCTGACCC CCTGAGCATGGTGGGCCCTAGCCAGGGCAGGAGCCCCAGCTATGCTAGC 97 ATGGACTCGGACGAGACGGGCTTCGAGCACTCGGGCCTGTGGGTGTCGGT GCTGGCGGGCCTGCTGCTGGGCGCGTGCCAGGCGCACCCGATCCCGGACTCG TCGCCGCTGCTGCAGTTCGGCGGCCAGGTGCGCCAGCGCTACCTGTACACGGA CGACGCGCAGCAGACGGAGGCGCACCTGGAGATCCGCGAGGACGGCACGGT GGGCGGCGCGGCGGACCAGTCGCCGGAGTCGCTGCTGCAGCTGAAGGCGCTG AAGCCGGGCGTGATCCAGATCCTGGGCGTGAAGACGTCGCGCTTCCTGTGCCA GCGCCCGGACGGCGCGCTGTACGGCTCGCTGCACTTCGACCCGGAGGCGTGC TCGTTCCGCGAGCTGCTGCTGGAGGACGGCTACAACGTGTACCAGTCGGAGG CGCACGGCCTGCCGCTGCACCTGCCGGGCAACAAGTCGCCGCACCGCGACCC GGCGCCGCGCGGCCCGGCGCGCTTCCTGCCGCTGCCGGGCCTGCCGCCGGCG CTGCCGGAGCCGCCGGGCATCCTGGCGCCGCAGCCGCCGGACGTGGGCTCGT CGGACCCGCTGTCGATGGTGGGCCCGTCGCAGGGCCGCTCGCCGTCGTACCGC CACGGCGAGGGCACGTTCACGTCGGACGTGTCGTCGTACCTGGAGGGCCAGG CGGCGCAGGAGTTCATCGCGTGGCTGGTGGACGGCCGCGGCCTGGTGCAGCC GCGCGGCTCGCGCAACGGCCCGGGCCCGTGGCAGGGCGGCCGCCGCAAGTTC CGCCGCCAGCGCCCGCGCCTGTCGCACAAGGGCCCGATGCCGTTC 98 ATGGACTCCGATGAGACCGGATTCGAACATAGCGGCCTGTGGGTGTCTGTG CTGGCTGGACTGCTGTTAGGGGCCTGCCAGGCCCACCCTATCCCTGATAGTAG CCCTCTGCTGCAGTTCGGGGGACAGGTGCGACAGCGGTACCTGTACACTGAC GACGCACAGCAGACAGAGGCCCATTTGGAGATTAGGGAAGATGGGACAGTGG GAGGCGCTGCCGACCAGAGTCCCGAGTCTCTGCTCCAGCTGAAGGCCCTGAA ACCTGGCGTGATCCAGATCCTGGGGGTGAAGACCTCCAGATTTCTGTGCCAGC GCCCTGACGGCGCTCTGTATGGGAGTCTGCATTTTGATCCTGAGGCTTGCTCCT TTCGCGAGCTGCTGCTCGAGGACGGCTACAATGTTTATCAGAGCGAAGCCCAC GGCCTGCCTCTGCATCTGCCAGGCAACAAATCCCCTCATAGAGATCCCGCACC ACGCGGGCCTGCACGCTTTCTGCCTCTCCCCGGGTTGCCCCCTGCCCTGCCTG AACCACCTGGAATCCTGGCCCCACAGCCTCCCGACGTCGGGTCCTCGGATCCC CTGTCTATGGTGGGGCCCTCTCAGGGGAGAAGCCCCTCATATAGGCACGGCGA AGGCACATTCACTAGTGACGTGAGCAGTTATCTGGAAGGCCAGGCTGCCCAGG AGTTCATCGCTTGGCTGGTGGATGGAAGAGGCCTGGTGCAGCCAAGGGGGAG CCGGAATGGCCCAGGCCCCTGGCAGGGAGGCAGAAGGAAGTTTCGACGCCAG AGACCCAGACTGTCTCATAAGGGCCCAATGCCTTTT 99 ATGGACTCCGACGAAACTGGATTCGAACACTCCGGACTGTGGGTCAGCGT TCTTGCGGGCCTGCTCCTCGGAGCCTGTCAGGCCCATCCAATTCCCGACAGCA GTCCACTCCTGCAGTTCGGGGGACAGGTCCGCCAGAGGTACCTGTACACTGAC GACGCCCAACAAACCGAAGCTCACCTCGAAATTCGGGAGGACGGTACTGTCG GGGGAGCAGCCGATCAGAGTCCTGAGTCTCTGCTCCAGCTGAAGGCATTGAA ACCAGGGGTCATTCAGATACTCGGCGTCAAAACCTCTCGGTTCCTTTGCCAGA GACCTGATGGCGCCCTCTATGGCAGCCTGCATTTCGACCCGGAAGCGTGTAGC TTTCGGGAACTTTTGCTGGAGGACGGATACAACGTGTACCAGTCTGAAGCCCA TGGACTGCCACTGCACCTCCCAGGGAATAAATCTCCTCATCGCGATCCTGCACC TCGCGGCCCAGCGAGATTCCTGCCATTGCCAGGCCTTCCCCCAGCCCTCCCGG AGCCACCTGGGATCCTTGCTCCACAACCACCTGACGTTGGATCATCAGACCCT CTCTCAATGGTCGGCCCAAGCCAAGGCCGCAGTCCTAGTTACAGGCATGGGGA AGGAACATTCACAAGCGACGTGTCCTCATACCTTGAGGGCCAGGCAGCCCAG GAATTTATTGCTTGGCTTGTCGATGGGCGAGGACTGGTGCAGCCAAGGGGGAG CAGAAATGGCCCCGGACCCTGGCAAGGCGGACGCCGGAAATTTCGGAGACAA AGACCGCGCTTGTCCCACAAAGGACCTATGCCATTT 100 ATGGATAGCGATGAAACCGGCTTTGAACACAGCGGCCTGTGGGTGTCTGTG CTTGCCGGCCTGCTGCTGGGGGCCTGCCAGGCCCACCCCATTCCCGACAGCAG CCCCCTGCTCCAGTTCGGCGGCCAGGTGCGGCAGAGGTATCTGTATACCGATG ATGCCCAGCAGACAGAAGCCCATCTGGAAATCAGGGAAGATGGCACCGTGGG CGGCGCCGCCGACCAGAGCCCCGAAAGCCTGCTGCAGCTGAAGGCCCTGAAA CCAGGCGTGATCCAGATTCTGGGCGTGAAAACCAGCAGGTTTCTGTGCCAGA GGCCCGATGGCGCCCTCTATGGCAGCCTTCATTTCGACCCCGAAGCATGCAGC TTTAGGGAGCTGCTGCTGGAAGATGGCTATAACGTATATCAGAGCGAGGCCCAT GGCCTGCCTCTGCATCTGCCCGGGAACAAAAGCCCCCACAGGGATCCCGCCCC CAGGGGACCCGCCAGGTTTCTTCCCTTGCCCGGCCTGCCTCCTGCACTGCCCG AGCCCCCCGGAATTCTGGCCCCCCAGCCCCCCGATGTGGGCAGCAGCGACCCC CTGAGCATGGTGGGCCCCAGCCAAGGCAGAAGCCCCTCATATAGGCATGGCGA AGGCACCTTTACCAGTGACGTGAGCAGCTACCTGGAAGGCCAGGCCGCCCAG GAATTCATTGCCTGGCTGGTGGATGGCCGAGGCCTGGTGCAGCCCAGAGGGA GTAGGAACGGCCCCGGACCCTGGCAGGGAGGCAGGAGGAAGTTTCGGAGGC AGAGACCCAGGCTGAGCCATAAAGGACCCATGCCCTTT 101 ATGGACTCGGACGAGACTGGGTTTGAGCACTCAGGCCTGTGGGTGTCGGT GCTCGCGGGCCTGCTGCTGGGCGCGTGCCAGGCGCATCCAATCCCGGACTCGT CGCCGCTGCTGCAGTTTGGCGGCCAGGTGCGCCAGCGCTACCTGTACACGGAC GACGCGCAGCAGACTGAGGCGCACCTGGAGATCCGCGAGGACGGCACGGTG GGCGGCGCGGCGGACCAGAGTCCGGAGTCGCTGCTGCAGCTGAAGGCGCTGA AGCCAGGAGTGATCCAGATCCTGGGAGTGAAGACCAGTCGCTTCCTGTGCCA GCGCCCGGACGGTGCCCTGTATGGCTCGCTGCACTTTGATCCGGAGGCATGTT CGTTCCGCGAGCTGCTGCTGGAGGACGGCTATAACGTCTACCAGTCAGAGGCG CACGGCCTGCCGCTGCACCTGCCGGGCAACAAGTCGCCGCACCGCGACCCAG CGCCGCGCGGCCCGGCTCGCTTCCTTCCGCTGCCGGGCCTGCCGCCGGCGCTT CCGGAGCCGCCGGGCATCCTGGCGCCGCAGCCGCCGGACGTCGGCTCGTCGG ACCCGCTGTCTATGGTGGGCCCGTCGCAGGGCCGCTCGCCATCGTACCGGCAC GGCGAGGGAACGTTTACGTCGGACGTCTCATCGTACCTGGAGGGCCAGGCGG CGCAGGAGTTCATCGCGTGGCTGGTGGACGGCCGCGGCCTGGTGCAGCCGCG CGGCAGTCGCAACGGACCGGGCCCATGGCAGGGCGGCCGCCGCAAGTTCCGC CGCCAGCGCCCGCGCCTGTCGCACAAGGGACCGATGCCTTTC 102 ATGGACAGCGATGAGACAGGATTCGAACATAGCGGCCTGTGGGTCTCCGTG CTGGCTGGACTGCTGTTAGGGGCCTGCCAGGCCCACCCTATCCCTGATAGTAG CCCTCTGCTGCAGTTTGGGGGACAGGTGCGACAGCGGTACCTGTACACTGACG ACGCTCAGCAGACAGAGGCCCACTTGGAGATTAGGGAAGATGGGACAGTTGG AGGCGCTGCCGACCAGTCGCCTGAGTCTCTGCTCCAGCTGAAGGCCCTGAAA CCTGGAGTGATCCAGATCCTGGGGGTGAAGACCTCCAGATTCCTGTGCCAGCG CCCTGACGGCGCCCTGTATGGGAGTCTGCACTTTGATCCTGAGGCTTGCTCCTT CCGCGAGCTGCTGTTGGAGGACGGCTATAACGTTTATCAGAGCGAAGCGCACG GCCTGCCTCTGCATCTGCCAGGCAACAAATCCCCTCATAGAGATCCTGCACCTC GCGGGCCTGCTCGCTTTCTGCCTTTGCCTGGGTTGCCCCCTGCCCTGCCTGAA CCACCTGGAATCCTGGCCCCTCAGCCGCCTGATGTTGGGTCTTCGGATCCCCTG TCTATGGTGGGGCCCTCTCAGGGGAGAAGCCCCTCATATAGGCACGGCGAAGG AACTTTCACTAGTGATGTGAGCAGTTATCTGGAAGGCCAGGCTGCCCAGGAGT TCATCGCTTGGCTGGTGGATGGAAGAGGCCTGGTGCAGCCAAGGGGGTCACG GAACGGTCCAGGCCCCTGGCAGGGAGGCAGAAGGAAGTTCCGTCGCCAGAG ACCCAGACTGTCTCATAAGGGCCCTATGCCTTTT 103 ATGGACAGCGACGAAACTGGATTCGAACACTCTGGCCTGTGGGTCAGCGT TCTCGCGGGCCTGCTCTTGGGAGCCTGTCAGGCCCATCCAATTCCTGACAGCA GTCCACTCCTGCAGTTTGGGGGACAGGTTCGCCAGAGGTACCTGTACACTGAC GACGCCCAACAAACAGAAGCTCACTTGGAAATCCGCGAGGACGGTACTGTTG GGGGAGCAGCTGATCAGAGTCCTGAGTCTCTGCTCCAGCTGAAGGCTTTGAA ACCAGGGGTTATTCAGATATTGGGCGTCAAAACCAGTCGGTTCCTTTGCCAGA GACCTGATGGCGCCCTCTATGGCAGCCTGCACTTTGATCCGGAAGCATGTAGCT TCCGCGAACTTTTGCTGGAAGATGGATATAACGTCTACCAGTCTGAAGCCCATG GACTGCCACTGCACTTGCCAGGGAATAAATCTCCTCACCGCGATCCTGCACCT CGCGGCCCAGCGAGATTCCTGCCTTTGCCAGGCCTTCCCCCAGCCCTTCCGGA GCCACCTGGGATCCTTGCTCCTCAACCACCAGACGTTGGATCATCAGACCCTC TCAGTATGGTCGGCCCAAGCCAAGGCCGCAGTCCTAGTTACAGGCATGGGGAA GGAACTTTCACATCAGATGTGTCCTCATACCTTGAGGGCCAGGCAGCCCAGGA ATTTATTGCTTGGCTTGTTGATGGGCGAGGACTGGTGCAGCCAAGGGGGAGCA GAAACGGTCCCGGACCCTGGCAAGGAGGACGGCGGAAATTTCGGAGACAAA GACCTCGCTTGTCCCATAAAGGACCTATGCCTTTT 104 ATGGATAGCGATGAAACCGGCTTTGAACATAGCGGCCTGTGGGTCTCCGTG CTTGCCGGCCTGCTGCTGGGGGCCTGCCAGGCCCACCCTATTCCTGACAGCAG CCCCCTGCTCCAGTTTGGCGGCCAGGTGCGGCAGAGGTACCTGTATACCGATG ATGCCCAGCAGACAGAAGCCCACCTGGAAATCAGGGAAGATGGCACGGTGGG CGGCGCCGCCGACCAGTCACCTGAAAGCCTGCTGCAGCTGAAGGCCCTGAAA CCTGGAGTGATCCAGATTCTGGGAGTGAAAACCAGCAGGTTCCTGTGCCAGA GACCTGATGGCGCCCTCTATGGCAGCCTTCACTTTGACCCTGAAGCATGCAGC TTTAGGGAGCTGCTGCTGGAAGATGGCTATAACGTTTATCAGAGCGAGGCCCA TGGCCTGCCTCTGCATCTGCCTGGGAACAAAAGCCCCCACAGGGATCCTGCCC CCAGGGGACCTGCCAGGTTTCTTCCCTTGCCCGGCCTGCCTCCTGCACTGCCC GAGCCCCCTGGAATTCTGGCCCCCCAGCCACCTGATGTGGGCAGCAGCGACCC CCTGAGCATGGTGGGCCCCAGCCAAGGCAGAAGCCCCTCATATAGGCATGGCG AAGGCACCTTTACCAGTGATGTGAGCAGCTACCTGGAAGGCCAGGCCGCCCA GGAATTTATTGCCTGGCTGGTGGATGGACGAGGCCTGGTGCAGCCCAGAGGGA GTAGGAACGGTCCCGGACCCTGGCAGGGAGGCAGGAGGAAGTTTCGGAGGC AGAGACCCAGGCTGAGCCATAAAGGACCCATGCCCTTT 105 ATGGACTCAGATGAGACTGGGTTTGAGCACTCAGGCCTGTGGGTGTCAGT GCTGGCAGGCCTGCTGCTGGGAGCATGCCAGGCTCATCCAATCCCAGACTCAT CACCACTGCTGCAGTTTGGAGGCCAGGTGAGACAGAGATACCTGTACACTGAT GATGCTCAGCAGACTGAGGCACACCTGGAGATCAGAGAGGATGGCACTGTTG GAGGAGCAGCAGACCAGTCACCAGAGTCACTGCTGCAGCTGAAGGCACTGA AGCCAGGAGTGATCCAGATCCTGGGAGTGAAGACTAGTAGATTCCTGTGCCAG AGACCAGATGGAGCCCTGTATGGCTCACTGCACTTTGATCCAGAGGCATGTAG TTTCAGAGAGCTGCTGCTGGAGGATGGCTATAATGTGTACCAGTCAGAGGCAC ATGGCCTGCCACTGCACCTGCCAGGCAACAAGTCACCACATAGAGACCCAGC ACCTAGAGGCCCAGCAAGATTCCTTCCACTGCCAGGCCTGCCACCAGCACTTC CAGAGCCACCAGGCATCCTGGCACCTCAGCCACCAGATGTGGGCTCATCAGAC CCACTAAGTATGGTGGGCCCATCACAGGGCAGATCACCATCATACAGGCATGG AGAGGGAACTTTTACTTCAGATGTGTCATCATACCTGGAGGGCCAGGCAGCAC AGGAGTTTATTGCATGGCTGGTGGATGGCAGAGGCCTGGTGCAGCCTAGAGGC TCAAGAAATGGCCCAGGTCCATGGCAGGGAGGCAGAAGAAAGTTCAGAAGA CAGAGACCTAGACTGTCACACAAGGGACCTATGCCTTTC 106 ATGGACTCTGATGAGACAGGATTTGAACACTCTGGCCTGTGGGTCAGTGTG CTGGCTGGACTGCTGTTAGGGGCCTGCCAGGCCCACCCTATCCCTGATAGTAG CCCTCTGCTGCAGTTTGGGGGACAGGTGAGACAGAGATACCTGTACACTGATG ATGCTCAGCAGACAGAGGCCCACTTGGAGATTAGGGAAGATGGGACAGTTGG AGGAGCTGCTGACCAGAGTCCTGAGTCTCTGCTCCAGCTGAAGGCCCTGAAA CCTGGAGTGATCCAGATCCTGGGGGTGAAGACCTCCAGATTCCTGTGCCAGAG ACCTGATGGAGCCCTGTATGGGAGTCTGCACTTTGATCCTGAGGCTTGCTCCTT CAGAGAGCTGCTGTTGGAGGATGGCTATAATGTTTATCAGTCTGAAGCCCATGG CCTGCCTCTGCATCTGCCAGGCAACAAATCCCCTCATAGAGATCCTGCACCTAG AGGGCCTGCTAGATTTCTGCCTTTGCCTGGGTTGCCCCCTGCCCTGCCTGAACC ACCTGGAATCCTGGCCCCTCAGCCTCCTGATGTTGGGTCTTCAGATCCCCTGTC TATGGTGGGGCCCTCTCAGGGGAGAAGCCCCTCATATAGGCATGGAGAAGGAA CTTTCACTAGTGATGTGAGCAGTTATCTGGAAGGCCAGGCTGCCCAGGAGTTT ATTGCTTGGCTGGTGGATGGAAGAGGCCTGGTGCAGCCAAGGGGGTCAAGAA ATGGCCCAGGCCCCTGGCAGGGAGGCAGAAGGAAGTTCAGAAGACAGAGAC CCAGACTGTCTCATAAGGGCCCTATGCCTTTT 107 ATGGACTCTGATGAAACTGGATTTGAACACTCTGGCCTGTGGGTCTCTGTT TTGGCAGGCCTGCTCTTGGGAGCCTGTCAGGCCCATCCAATTCCTGACAGCAG TCCACTCCTGCAGTTTGGGGGACAGGTTAGACAGAGGTACCTGTACACTGATG ATGCCCAACAAACAGAAGCTCACTTGGAAATCAGAGAGGATGGTACTGTTGG GGGAGCAGCTGATCAGAGTCCTGAGTCTCTGCTCCAGCTGAAGGCTTTGAAA CCAGGGGTTATTCAGATATTGGGAGTCAAAACCAGTAGATTCCTTTGCCAGAG ACCTGATGGAGCCCTCTATGGCAGCCTGCACTTTGATCCAGAAGCATGTAGCTT CAGAGAACTTTTGCTGGAAGATGGATATAATGTGTACCAGTCTGAAGCCCATG GACTGCCACTGCACTTGCCAGGGAATAAATCTCCTCATAGAGATCCTGCACCTA GAGGCCCAGCAAGATTCCTGCCTTTGCCAGGCCTTCCCCCAGCCCTTCCAGAG CCACCTGGGATCCTTGCTCCTCAACCACCAGATGTTGGATCATCAGACCCTCTC AGTATGGTTGGCCCAAGCCAAGGCAGAAGTCCTAGTTACAGGCATGGGGAAG GAACTTTCACATCAGATGTGTCCTCATACCTTGAGGGCCAGGCAGCCCAGGAA TTTATTGCTTGGCTTGTTGATGGAAGAGGACTGGTGCAGCCAAGGGGGAGCAG AAATGGCCCTGGACCCTGGCAAGGAGGAAGAAGAAAATTTAGAAGACAAAG ACCTAGATTGTCCCATAAAGGACCTATGCCTTTT 108 ATGGATTCTGATGAAACAGGCTTTGAACACTCTGGCCTGTGGGTCAGTGTG CTTGCTGGCCTGCTGCTGGGGGCCTGCCAGGCCCACCCTATTCCTGACAGCAG CCCCCTGCTCCAGTTTGGAGGCCAGGTGAGACAGAGGTACCTGTATACTGATG ATGCCCAGCAGACAGAAGCCCACCTGGAAATCAGGGAAGATGGAACAGTTGG AGGAGCTGCTGACCAGTCACCTGAAAGCCTGCTGCAGCTGAAGGCCCTGAAA CCTGGAGTGATCCAGATTCTGGGAGTGAAAACCAGCAGGTTCCTGTGCCAGA GACCTGATGGAGCCCTCTATGGCAGCCTTCACTTTGACCCTGAAGCATGCAGC TTTAGGGAGCTGCTGCTGGAAGATGGCTATAATGTATATCAGTCTGAGGCCCAT GGCCTGCCTCTGCATCTGCCTGGGAACAAAAGCCCCCACAGGGATCCTGCCCC CAGGGGACCTGCCAGGTTTCTTCCCTTGCCTGGCCTGCCTCCTGCACTGCCTG AGCCCCCTGGAATTCTGGCCCCCCAGCCACCTGATGTGGGCAGCTCTGACCCC CTGAGCATGGTGGGCCCCAGCCAAGGCAGAAGCCCCTCATATAGGCATGGAGA AGGCACCTTTACCAGTGATGTGAGCAGCTACCTGGAAGGCCAGGCTGCCCAG GAATTTATTGCCTGGCTGGTGGATGGAAGAGGCCTGGTGCAGCCCAGAGGGA GTAGGAATGGCCCTGGACCCTGGCAGGGAGGCAGGAGGAAGTTTAGAAGGCA GAGACCCAGGCTGAGCCATAAAGGACCCATGCCCTTT 109 ATGATCCCGGCGAAGGACATGGCGAAGGTGATGATCGTGATGCTGGCGATC TGCTTCCTGACGAAGTCGGACGGCAAGTCGGTGAAGAAGCGCTCGGTGTCGG AGATCCAGCTGATGCACAACCTGGGCAAGCACCTGAACTCGATGGAGCGCGT GGAGTGGCTGCGCAAGAAGCTGCAGGACGTGCACAACTTCCGCCACGGCGAG GGCACGTTCACGTCGGACGTGTCGTCGTACCTGGAGGGCCAGGCGGCGCAGG AGTTCATCGCGTGGCTGGTGGACGGCCGCGGCCTGGTGCAGCCGCGCGGCTC GCGCAACGGCCCGGGCCCGTGGCAGGGCGGCCGCCGCAAGTTCCGCCGCCAG CGCCCGCGCCTGTCGCACAAGGGCCCGATGCCGTTC 110 ATGATTCCAGCCAAAGACATGGCCAAAGTGATGATTGTGATGCTGGCCATC TGCTTTCTGACCAAGTCCGACGGAAAGAGCGTGAAGAAACGGAGCGTGAGCG AGATCCAGCTCATGCACAACCTGGGGAAGCACCTGAATTCTATGGAGCGGGTG GAGTGGCTGAGGAAGAAGCTGCAGGACGTGCACAATTTCCGGCACGGCGAAG GAACCTTCACCAGCGACGTGAGCTCTTACCTGGAGGGCCAGGCCGCCCAGGA GTTCATCGCCTGGCTGGTGGATGGCAGAGGTCTGGTGCAGCCAAGGGGTTCCC GGAACGGGCCAGGCCCTTGGCAGGGCGGCAGGAGAAAGTTCAGGCGCCAGA GGCCCAGACTGTCCCACAAGGGGCCCATGCCTTTC 111 ATGATCCCTGCGAAGGACATGGCAAAGGTTATGATTGTGATGCTGGCAATTT GCTTCTTGACCAAGAGTGATGGTAAAAGCGTAAAAAAACGGTCCGTATCTGAG ATCCAACTGATGCATAATCTGGGGAAGCACCTGAACAGCATGGAGAGAGTGGA GTGGCTGAGGAAGAAGCTGCAGGATGTGCATAACTTCCGACACGGGGAGGGC ACCTTCACAAGCGACGTTTCCTCCTACCTTGAGGGCCAGGCTGCTCAGGAGTT CATCGCCTGGCTCGTGGATGGTCGGGGGCTCGTGCAGCCACGAGGGTCTAGGA ATGGTCCGGGGCCTTGGCAAGGCGGAAGGCGCAAATTCCGGCGACAGAGACC CAGACTGTCACACAAAGGCCCTATGCCATTT 112 ATGATCCCCGCCAAGGATATGGCCAAGGTGATGATCGTGATGCTGGCCATCT GCTTCCTGACCAAGAGCGACGGCAAGAGCGTGAAGAAGAGGAGCGTGAGCG AGATCCAGCTGATGCACAACCTGGGCAAGCACCTGAACAGCATGGAGAGGGT GGAGTGGCTGAGGAAGAAGCTGCAGGACGTGCACAACTTCAGGCACGGCGA GGGCACCTTCACCAGCGACGTGAGCAGCTACCTGGAGGGCCAGGCCGCCCAG GAGTTCATCGCCTGGCTGGTAGACGGAAGGGGCCTGGTGCAGCCCAGGGGCA GCAGGAATGGACCCGGACCCTGGCAAGGCGGTAGGAGGAAGTTCAGGCGAC AGAGGCCCAGGCTGAGCCACAAGGGCCCCATGCCCTTC 113 ATGATACCGGCGAAGGACATGGCGAAGGTGATGATAGTGATGCTGGCGATC TGCTTCCTGACGAAGTCGGACGGCAAGTCGGTGAAGAAGCGCTCGGTTTCGG AGATCCAGCTGATGCATAACCTGGGCAAGCACCTGAATAGTATGGAGCGCGTG GAGTGGCTGCGCAAGAAGCTGCAAGATGTGCATAACTTTAGGCACGGCGAGG GAACGTTTACGTCGGACGTCTCATCGTACCTGGAGGGCCAGGCGGCGCAGGA GTTCATCGCGTGGCTGGTGGACGGCCGCGGCCTGGTGCAGCCGCGCGGCAGT CGCAACGGACCGGGCCCATGGCAGGGCGGCCGCCGCAAGTTCCGCCGCCAGC GCCCGCGCCTGTCGCACAAGGGACCGATGCCTTTC 114 ATGATTCCAGCCAAAGACATGGCCAAAGTGATGATAGTGATGCTGGCCATC TGCTTTCTGACCAAGTCCGACGGAAAGTCCGTGAAGAAACGGTCCGTGAGCG AGATCCAGCTCATGCATAACCTGGGGAAGCACCTGAATTCTATGGAGCGCGTG GAGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAATTTCAGGCACGGCGAAG GAACCTTCACCAGCGATGTGAGCTCTTACCTGGAGGGCCAGGCCGCCCAGGA GTTCATCGCCTGGCTGGTGGATGGCAGAGGTCTGGTGCAGCCAAGGGGTTCAC GGAACGGTCCAGGCCCTTGGCAGGGCGGCAGGAGAAAGTTCAGGCGCCAGA GGCCCAGACTGTCCCACAAGGGGCCCATGCCTTTC 115 ATGATCCCTGCGAAGGACATGGCAAAGGTTATGATAGTGATGCTGGCAATT TGCTTCTTGACCAAGAGTGATGGTAAATCCGTGAAAAAACGGTCCGTATCTGA GATCCAACTGATGCATAATCTGGGGAAGCACCTGAACAGCATGGAGAGAGTGG AGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAACTTCAGGCACGGGGAGGG CACCTTCACATCAGACGTTTCCTCCTACCTTGAGGGCCAGGCTGCTCAGGAGT TCATCGCCTGGTTGGTGGATGGTCGCGGGCTCGTGCAGCCGCGAGGGTCTAGG AACGGTCCGGGGCCTTGGCAAGGAGGAAGGCGCAAATTCCGCCGACAGAGA CCCAGACTGTCACATAAAGGCCCTATGCCTTTT 116 ATGATCCCTGCCAAGGATATGGCCAAGGTGATGATAGTGATGCTGGCCATCT GCTTCCTGACCAAGAGCGACGGCAAGTCCGTGAAGAAGAGGTCCGTGAGCGA GATCCAGCTGATGCATAACCTGGGCAAGCACCTGAACAGCATGGAGAGGGTG GAGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAACTTCAGGCACGGCGAGG GCACCTTCACCAGCGATGTGAGCAGCTACCTGGAGGGCCAGGCCGCCCAGGA GTTCATCGCCTGGCTGGTCGACGGAAGGGGCCTGGTGCAGCCCAGGGGCAGC AGGAACGGTCCCGGACCCTGGCAAGGCGGTAGGAGGAAGTTCAGGCGACAG AGGCCCAGGCTGAGCCACAAGGGCCCCATGCCCTTC 117 ATGATACCAGCAAAGGACATGGCAAAGGTGATGATTGTCATGCTGGCAATC TGCTTCCTGACTAAGTCAGATGGCAAGTCAGTGAAGAAGAGATCAGTTTCAGA GATCCAGCTGATGCATAACCTGGGCAAGCACCTGAATAGTATGGAGAGAGTGG AGTGGCTGAGAAAGAAGCTGCAAGATGTGCATAACTTTAGACATGGAGAGGG AACTTTTACTTCAGATGTGTCATCATACCTGGAGGGCCAGGCAGCACAGGAGT TTATTGCATGGCTGGTGGATGGCAGAGGCCTGGTGCAGCCTAGAGGCTCAAGA AATGGCCCAGGTCCATGGCAGGGAGGCAGAAGAAAGTTCAGAAGACAGAGA CCTAGACTGTCACACAAGGGACCTATGCCTTTC 118 ATGATTCCAGCCAAAGACATGGCCAAAGTGATGATAGTGATGCTGGCCATC TGCTTTCTGACCAAGTCAGATGGAAAGAGTGTCAAGAAAAGGAGTGTCTCTG AGATCCAGCTCATGCATAACCTGGGGAAGCACCTGAATTCTATGGAGAGAGTG GAGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAATTTCAGACATGGAGAAG GAACCTTCACCTCTGATGTGAGCTCTTACCTGGAGGGCCAGGCTGCCCAGGAG TTTATTGCCTGGCTGGTGGATGGCAGAGGTCTGGTGCAGCCAAGGGGTTCAAG GAATGGGCCAGGCCCTTGGCAGGGAGGCAGGAGAAAGTTCAGGAGACAGAG GCCCAGACTGTCCCACAAGGGGCCCATGCCTTTC 119 ATGATCCCTGCAAAGGACATGGCAAAGGTTATGATAGTGATGCTGGCAATT TGCTTCTTGACCAAGAGTGATGGTAAATCTGTCAAAAAAAGATCTGTTTCTGA GATCCAACTGATGCATAATCTGGGGAAGCACCTGAACAGCATGGAGAGAGTGG AGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAACTTCAGACATGGGGAGGG CACCTTCACATCTGATGTTTCCTCCTACCTTGAGGGCCAGGCTGCTCAGGAGTT TATTGCCTGGTTGGTGGATGGTAGAGGGTTGGTGCAGCCAAGAGGGTCTAGGA ATGGTCCAGGGCCTTGGCAAGGAGGAAGGAGAAAATTCAGAAGACAGAGAC CCAGACTGTCACATAAAGGCCCTATGCCTTTT 120 ATGATCCCTGCCAAGGATATGGCCAAGGTGATGATTGTCATGCTGGCCATCT GCTTCCTGACCAAGTCTGATGGCAAGAGTGTCAAGAAGAGGAGTGTCTCTGA GATCCAGCTGATGCATAACCTGGGCAAGCACCTGAACAGCATGGAGAGGGTG GAGTGGCTGAGGAAGAAGCTGCAAGATGTGCATAACTTCAGGCATGGAGAGG GCACCTTCACCTCTGATGTGAGCAGCTACCTGGAGGGCCAGGCTGCCCAGGA GTTTATTGCCTGGCTGGTAGATGGAAGGGGCCTGGTGCAGCCCAGGGGCAGCA GGAATGGACCTGGACCCTGGCAAGGAGGTAGGAGGAAGTTCAGGAGACAGA GGCCCAGGCTGAGCCACAAGGGCCCCATGCCCTTC

Claims

CLAIMS What is claimed is: 1) A DNA cassette for use in gene therapy treatment of mammalian pathologies, intended for delivery via viral or non-viral vectors, which has been optimized to exclude one or more sequences from a set of DNA sensor binding sites by base substitution to enhance hypoimmunogenicity and / or potency via modulation of inflammation, intracellular DNA sensing, or epigenetic regulation. 2) Sequences in Claim 1, which are reactive to DNA sensors that activate the innate immune response. 3) Sequences in Claim 1, which are reactive to DNA sensors that are intracellular DNA sensors. 4) Sequences in Claim 1, which are reactive to DNA sensors capable of promoting epigenetic silencing. 5) Sequences in Claim 1, which are bound by intracellular proteins, which can in turn activate the innate immune response. 6) Sequences in Claim 1, which are bound by intracellular proteins, which can in turn activate intracellular DNA sensors. 7) Sequences in Claim 1, which are bound by intracellular proteins, which can in turn promote formation of heterochromatin. 8) Sequences in Claim 1, which are bound by intracellular proteins, which can in turn promote DNA methylation. 9) Sequences in Claim 1, which are bound by intracellular proteins, which can in turn promote histone modifications that lead to a reduction in the level of gene expression. 10) Sequences in Claim 1, which are TLR binding sites. 11) Sequences in Claim 1, which are TLR9 binding sites. 12) Sequences in Claim 1, which are binding sites of the cGAS-STING signaling pathway. 13) Sequences in Claim 1, which are binding sites of DNA Methyltransferases. 14) Sequences in Claim 1, which are binding sites of DNA methyltransferase 1. 15) Sequences in Claim 1, which are binding sites of DNA methyltransferase 3A. 16) Sequences in Claim 1, which are binding sites of DNA methyltransferase 3B. 17) Sequences in Claim 1, which are binding sites of DNA methyltransferase 3L.18) Sequences in Claim 1, which are binding sites of DNA methyltransferase 2. 19) Sequences in Claim 1, which are DNA binding sites of SUV39H1, SUV39H2, SETDB1, MeCP2, SIRT1, CBX Proteins, Lamin B Receptor, Condensin Complex or proteins interacting with said proteins or protein complexes. 20) Sequences in Claim 1, which mimic RNA binding sites of intracellular RNA sensors. 21) Genetic cassettes in Claim 1, which are double stranded DNA cassettes. 22) Genetic cassettes in Claim 1, which are partially double stranded DNA cassettes. 23) Genetic cassettes in Claim 1, which are single stranded DNA cassettes. 24) Genetic cassettes in Claim 1, which are linear DNA cassettes with or without covalently closed ends. 25) Genetic cassettes in Claim 1, which are circular DNA cassettes. 26) Genetic cassettes in Claim 1, which are DNA / RNA hybrids. 27) Genetic cassettes in Claim 1, which are DNA cassettes where at least some of the DNA has undergone chemical modification. 28) Genetic cassettes in Claim 1, which are DNA-peptide or DNA-protein hybrids. 29) Exclusion in Claim 1, which is a single nucleotide substitution or modification that prevents 100% homology with the original binding site sequence. 30) Exclusion in Claim 1, which is a two-nucleotide substitution or modification that reduces homology with the original binding site sequence. 31) Exclusion in Claim 1, which is a three-nucleotide substitution or modification that reduces homology with the original binding site sequence. 32) Exclusion in Claim 1, which is a substitution of one to three nucleotides, that reduces homology with the original binding site sequence, without creating a new reactive sequence. 33) Exclusion in Claim 1, which is a reduction in the total number of reactive sequences within the genetic cassette. 34) Exclusion in Claim 1, which is complete elimination of 100% matching reactive sequences within the genetic cassette. 35) Sequences in Claim 1, which are derived from one or more Reactive Sequences listed in the Examples. 36) Viral vectors in Claim 1, which are comprised at least in part from at least a part of adeno-associated viruses, lentiviruses, retroviruses, herpes simplex viruses,adenoviruses, anneloviruses, enteroviruses, pox viruses, or other viruses known to be associated with humans or mammals. 37) Non-viral vectors in Claim 1, which are comprised at least in part from at least a part of lipid nanoparticles, polymeric nanoparticles, metallic nanoparticles, liposomes, exosomes, virus like particles, cell membranes, lipids, or peptide complexes. 38) Non-viral vectors in Claim 1, which are physical or chemical means of introducing genetic cassettes into mammalian cells. 39) A reactive sequence in any claim, which is derived from at least 80% of a given sequences listed in the Examples. 40) A reactive sequence in any claim, which is capable of binding intracellular DNA sensors, components of proinflammatory complexes, or components of epigenetic silencing machinery. 41) A method for constructing therapeutic DNA sequences in Claim 1, where original sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2. 42) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in the forward strand. 43) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude that are present in the construct. 44) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in the reverse strand. 45) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in both forward and reverse strands. 46) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in the coding region by identifying nucleotides that can be substituted in such a way that the highest frequency codon is selected for a given amino acid without affecting the amino acid encoded in the original consensus sequence.47) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in the coding region by identifying nucleotides that can be substituted in such a way that a codon with a similar frequency to the original codon is selected for a given amino acid without affecting the amino acid encoded in the original consensus sequence. 48) A method for constructing therapeutic DNA sequences in Claim 1, where consensus sequences are modified by substituting one or more nucleotides to reduce the number of sequences to exclude from Example 2 in the non-coding region by substituting nucleotides that are not essential to regulatory sequence functionality. 49) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 22 is GCA and / or Codon # 23 is ACA and / or Codon # 25 is ATT and / or Codon # 37 is ACT and / or Codon # 52 is TCA and / or Codon # 56 is TTT and / or Codon # 65 is GTC and / or Codon # 66 is GGT and / or Codon # 70 is TAT and / or Codon # 73 is AGG and / or Codon # 81 is AGA and / or Codon # 83 is CCA . 50) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 12 is GTC and / or Codon # 14 is TCA and / or Codon # 16 is GCA and / or Codon # 22 is GCA and / or Codon # 23 is ACT and / or Codon # 24 is CCA and / or Codon # 25 is ATT and / or Codon # 27 is TCA and / or Codon # 33 is AGA and / or Codon # 37 is ACT and / or Codon # 38 is GCC and / or Codon # 39 is ACT and / or Codon # 40 is TGT and / or Codon # 41 is GCA and / or Codon # 42 is ACT and / or Codon # 44 is AGA and / or Codon # 46 is GCA and / or Codon # 52 is TCA and / or Codon # 53 is TCA and / or Codon # 56 is TTT and / or Codon # 57 is GGA and / or Codon # 58 is GCA and / or Codon # 61 is TCA and / or Codon # 62 is TCA and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 65 is GTT and / or Codon # 66 is GGA and / or Codon # 67 is TCA and / or Codon # 69 is ACT and / or Codon # 70 is TAT and / or Codon # 73 is AGA and / or Codon # 74 is AAT and / or Codon # 75 is GCA and / or Codon # 81 is AGA and / or Codon # 83 is CCA and / or Codon # 88 is CCA . 51) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 14 is TCC and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 37 is ACT and / or Codon # 51 is CAT and / or Codon # 63 is ACT and / or Codon # 65 is GTC and / or Codon # 74 is AAC and / or Codon # 75 is GCA and / or Codon # 80 is AAG and / or Codon # 81 is AGA .52) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 14 is AGT and / or Codon # 15 is GTT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 37 is ACT and / or Codon # 44 is AGA and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 70 is TAT and / or Codon # 75 is GCT and / or Codon # 76 is GTT and / or Codon # 80 is AAG and / or Codon # 81 is AGA . 53) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 13 is CTC and / or Codon # 19 is CAC and / or Codon # 24 is CCT and / or Codon # 30 is GTT and / or Codon # 58 is GCT and / or Codon # 64 is AAC and / or Codon # 81 is AGA . 54) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 13 is CTC and / or Codon # 19 is CAC and / or Codon # 24 is CCT and / or Codon # 30 is GTT and / or Codon # 44 is AGA and / or Codon # 58 is GCT and / or Codon # 74 is AAT and / or Codon # 81 is AGA and / or Codon # 88 is CCA . 55) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 14 is TCC and / or Codon # 24 is CCT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 63 is ACT and / or Codon # 65 is GTT and / or Codon # 70 is TAT and / or Codon # 74 is AAC and / or Codon # 75 is GCA . 56) A therapeutic in Claim 1, which is an Amylin peptide encoded by a nucleic acid, such that Codon # 11 is ATT and / or Codon # 12 is GTC and / or Codon # 14 is AGT and / or Codon # 15 is GTT and / or Codon # 24 is CCT and / or Codon # 25 is ATT and / or Codon # 34 is AAG and / or Codon # 40 is TGT and / or Codon # 51 is CAT and / or Codon # 56 is TTT and / or Codon # 57 is GGA and / or Codon # 63 is ACT and / or Codon # 64 is AAT and / or Codon # 65 is GTT and / or Codon # 70 is TAT and / or Codon # 75 is GCT and / or Codon # 76 is GTT . 57) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 18 is CTC and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 40 is TTT and / or Codon # 57 is ACT and / or Codon # 76 is AGT and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACC and / or Codon # 99 is AGT and / or Codon # 108 is GGT and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / orCodon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 137 is TCA and / or Codon # 156 is CCA and / or Codon # 162 is GCT and / or Codon # 165 is CTT and / or Codon # 174 is CTT and / or Codon # 188 is GTC and / or Codon # 195 is TCT and / or Codon # 205 is CCT and / or Codon # 207 is TAT . 58) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 3 is TCA and / or Codon # 4 is GAT and / or Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 16 is TCA and / or Codon # 19 is GCA and / or Codon # 24 is GGA and / or Codon # 25 is GCA and / or Codon # 28 is GCT and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 32 is CCA and / or Codon # 34 is TCA and / or Codon # 35 is TCA and / or Codon # 36 is CCA and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 57 is ACT and / or Codon # 59 is GCA and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 68 is ACT and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCA and / or Codon # 73 is GCA and / or Codon # 76 is TCA and / or Codon # 77 is CCA and / or Codon # 79 is TCA and / or Codon # 85 is GCA and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACT and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 106 is CCA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 113 is TCA and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 122 is AGT and / or Codon # 124 is AGA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCA and / or Codon # 139 is GCA and / or Codon # 140 is CAT and / or Codon # 143 is CCA and / or Codon # 147 is CCA and / or Codon # 151 is TCA and / or Codon # 152 is CCA and / or Codon # 153 is CAT and / or Codon # 154 is AGA and / or Codon # 156 is CCA and / or Codon # 157 is GCA and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 161 is CCA and / or Codon # 162 is GCA and / or Codon # 163 is AGA and / or Codon # 165 is CTT and / or Codon # 166 is CCA and / or Codon # 168 is CCA and / or Codon # 171 is CCA and / or Codon # 172 is CCA and / or Codon # 173 is GCAand / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 177 is CCA and / or Codon # 178 is CCA and / or Codon # 182 is GCA and / or Codon # 183 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 190 is TCA and / or Codon # 191 is TCA and / or Codon # 193 is CCA and / or Codon # 194 is CTA and / or Codon # 195 is AGT and / or Codon # 199 is CCA and / or Codon # 200 is TCA and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 206 is TCA and / or Codon # 207 is TAT and / or Codon # 208 is GCA and / or Codon # 209 is TCA . 59) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACA and / or Codon # 10 is CAT and / or Codon # 16 is TCC and / or Codon # 32 is CCT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 73 is GCA and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 110 is CTC and / or Codon # 115 is CAC and / or Codon # 118 is CCT and / or Codon # 122 is AGT and / or Codon # 133 is AAC and / or Codon # 134 is GTC and / or Codon # 139 is GCG and / or Codon # 147 is CCT and / or Codon # 172 is CCT and / or Codon # 186 is CCG and / or Codon # 188 is GTC and / or Codon # 190 is TCG and / or Codon # 199 is CCA . 60) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 6 is ACA and / or Codon # 10 is CAT and / or Codon # 16 is AGT and / or Codon # 19 is GCT and / or Codon # 32 is CCT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 73 is GCT and / or Codon # 77 is CCT and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 110 is CTC and / or Codon # 111 is TAT and / or Codon # 115 is CAC and / or Codon # 118 is CCT and / or Codon # 122 is AGT and / or Codon # 140 is CAT and / or Codon # 147 is CCT and / or Codon # 163 is AGA and / or Codon # 172 is CCT and / or Codon # 187 is GAT and / or Codon # 191 is TCT and / or Codon # 197 is GTT and / or Codon # 199 is CCA . 61) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 10 is CAT and / or Codon # 15 is GTC and / or Codon # 23 is TTG and / or Codon # 31 is ATA and / or Codon # 32 is CCT and / or Codon # 54 is GCT and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 91 is ATT and / or Codon # 94 is TTG and / or Codon # 100 is CGC and / or Codon # 105 is CGC and / or Codon # 111 isTAT and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 120 is GCA and / or Codon # 122 is AGT and / or Codon # 123 is TTC and / or Codon # 124 is CGC and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAC and / or Codon # 134 is GTT and / or Codon # 139 is GCG and / or Codon # 156 is CCT and / or Codon # 157 is GCT and / or Codon # 158 is CCA and / or Codon # 160 is GGA and / or Codon # 161 is CCT and / or Codon # 165 is TTG and / or Codon # 178 is CCA and / or Codon # 183 is CCT and / or Codon # 188 is GTC and / or Codon # 204 is TCA . 62) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 4 is GAT and / or Codon # 8 is TTT and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is TCT and / or Codon # 17 is GTT and / or Codon # 18 is TTG and / or Codon # 23 is TTG and / or Codon # 31 is ATA and / or Codon # 32 is CCT and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 68 is ACT and / or Codon # 72 is GCT and / or Codon # 73 is GCA and / or Codon # 77 is CCT and / or Codon # 91 is ATT and / or Codon # 94 is TTG and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 120 is GCA and / or Codon # 122 is AGT and / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 140 is CAT and / or Codon # 156 is CCT and / or Codon # 157 is GCT and / or Codon # 158 is CCA and / or Codon # 160 is GGA and / or Codon # 161 is CCT and / or Codon # 165 is TTG and / or Codon # 173 is GCA and / or Codon # 178 is CCA and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 191 is TCT and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 207 is TAT . 63) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 8 is TTT and / or Codon # 12 is GGC and / or Codon # 16 is TCC and / or Codon # 28 is GCT and / or Codon # 39 is CAG and / or Codon # 40 is TTT and / or Codon # 51 is ACT and / or Codon # 68 is ACG and / or Codon # 72 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 118 is CCT and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 isTAT and / or Codon # 139 is GCG and / or Codon # 172 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 207 is TAT . 64) A therapeutic in Claim 1, which is an FGF21 peptide encoded by a nucleic acid, such that Codon # 4 is GAT and / or Codon # 6 is ACA and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 12 is GGC and / or Codon # 16 is AGT and / or Codon # 28 is GCT and / or Codon # 39 is CAG and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 51 is ACT and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 108 is GGA and / or Codon # 118 is CCT and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCT and / or Codon # 140 is CAT and / or Codon # 163 is AGA and / or Codon # 172 is CCT and / or Codon # 182 is GCA and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 191 is TCT and / or Codon # 207 is TAT . 65) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 2 is AAA and / or Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 17 is GGT and / or Codon # 31 is CGA and / or Codon # 34 is TCA and / or Codon # 35 is GCA and / or Codon # 38 is GCA and / or Codon # 49 is GAA and / or Codon # 56 is GGA and / or Codon # 58 is TTT and / or Codon # 62 is TAT and / or Codon # 70 is CGG and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 91 is CGG and / or Codon # 95 is TTT and / or Codon # 97 is CGG and / or Codon # 101 is GGA and / or Codon # 103 is TTT and / or Codon # 107 is GTC and / or Codon # 108 is TCA and / or Codon # 132 is TTT and / or Codon # 138 is ATA and / or Codon # 145 is CGG and / or Codon # 149 is GGT and / or Codon # 157 is ACT . 66) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 2 is AAA and / or Codon # 3 is TCA and / or Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCA and / or Codon # 11 is TTT and / or Codon # 12 is GTC and / or Codon # 17 is GGT and / or Codon # 18 is TCA and / or Codon # 21 is AGA and / or Codon # 22 is TCA and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 31 is AGA and / or Codon # 32 is AGT and / or Codon # 34 is TCA and / or Codon # 35 is GCA and / or Codon # 36 is TCA and / or Codon # 38 is GCA and / or Codon # 40is CCA and / or Codon # 42 is TCA and / or Codon # 44 is CCA and / or Codon # 48 is AAT and / or Codon # 52 is AGA and / or Codon # 54 is TCA and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 58 is TTT and / or Codon # 59 is ACT and / or Codon # 60 is TCA and / or Codon # 62 is TAT and / or Codon # 63 is TCA and / or Codon # 68 is AGT and / or Codon # 69 is AGA and / or Codon # 70 is AGA and / or Codon # 71 is GCA and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGA and / or Codon # 85 is AGA and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 89 is GCA and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 97 is AGA and / or Codon # 98 is CAT and / or Codon # 99 is GCA and / or Codon # 101 is GGA and / or Codon # 102 is ACT and / or Codon # 103 is TTT and / or Codon # 104 is ACT and / or Codon # 105 is TCA and / or Codon # 106 is GAT and / or Codon # 108 is TCA and / or Codon # 109 is TCA and / or Codon # 115 is GCA and / or Codon # 116 is GCA and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 121 is GCA and / or Codon # 127 is AGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 132 is TTT and / or Codon # 133 is CCA and / or Codon # 137 is GCA and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 144 is AGA and / or Codon # 145 is AGA and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 149 is GGA and / or Codon # 150 is AGT and / or Codon # 152 is TCA and / or Codon # 153 is GAT and / or Codon # 157 is ACT and / or Codon # 163 is GCA and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 174 is ACT and / or Codon # 177 is ACT and / or Codon # 179 is AGA . 67) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 34 is AGC and / or Codon # 49 is GAA and / or Codon # 51 is AAG and / or Codon # 53 is CAT and / or Codon # 59 is ACT and / or Codon # 60 is AGC and / or Codon # 75 is GTC and / or Codon # 83 is CGC and / or Codon # 91 is AGG and / or Codon # 95 is TTT and / or Codon # 99 is GCG and / or Codon # 105 is AGC and / or Codon # 106 is GAT and / or Codon # 127 is CGC and / or Codon # 137 is GCG and / or Codon # 138 is ATA and / or Codon # 164 is GCA . 68) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon #11 is TTT and / or Codon # 12 is GTC and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 30 is TCA and / or Codon # 31 is AGA and / or Codon # 34 is TCT and / or Codon # 38 is GCT and / or Codon # 42 is TCT and / or Codon # 48 is AAT and / or Codon # 51 is AAG and / or Codon # 52 is AGA and / or Codon # 53 is CAT and / or Codon # 59 is ACT and / or Codon # 60 is TCT and / or Codon # 69 is AGA and / or Codon # 70 is AGA and / or Codon # 75 is GTC and / or Codon # 83 is AGA and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 98 is CAT and / or Codon # 99 is GCT and / or Codon # 105 is TCT and / or Codon # 106 is GAT and / or Codon # 115 is GCT and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 127 is AGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 153 is GAT and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 177 is ACT . 69) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 12 is GTC and / or Codon # 26 is ACT and / or Codon # 32 is AGT and / or Codon # 44 is CCT and / or Codon # 48 is AAC and / or Codon # 68 is AGT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGG and / or Codon # 85 is CGC and / or Codon # 91 is CGG and / or Codon # 126 is GGG and / or Codon # 129 is AGA and / or Codon # 133 is CCT and / or Codon # 137 is GCG and / or Codon # 138 is ATA and / or Codon # 152 is AGC and / or Codon # 154 is GAG and / or Codon # 157 is ACT and / or Codon # 179 is CGC . 70) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon # 12 is GTC and / or Codon # 14 is TTG and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 32 is AGT and / or Codon # 34 is TCT and / or Codon # 38 is GCT and / or Codon # 44 is CCT and / or Codon # 60 is TCT and / or Codon # 68 is AGT and / or Codon # 69 is AGA and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 81 is ACT and / or Codon # 83 is AGG and / or Codon # 85 is AGA and / or Codon # 89 is GCA and / or Codon # 91 is AGA and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 97 is AGA and / or Codon # 105 is TCA and / or Codon # 106 is GAT and / or Codon # 115 is GCT and / or Codon # 126 is GGG and / or Codon # 127 isAGA and / or Codon # 129 is AGA and / or Codon # 130 is AGA and / or Codon # 133 is CCT and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 139 is GTT and / or Codon # 146 is CAT and / or Codon # 147 is GCA and / or Codon # 148 is GAT and / or Codon # 152 is TCT and / or Codon # 154 is GAG and / or Codon # 157 is ACT and / or Codon # 164 is GCA and / or Codon # 165 is AGA and / or Codon # 179 is AGA . 71) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTC and / or Codon # 26 is ACT and / or Codon # 44 is CCT and / or Codon # 49 is GAA and / or Codon # 53 is CAT and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 62 is TAT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 84 is AAT and / or Codon # 95 is TTT and / or Codon # 99 is GCT and / or Codon # 133 is CCT . 72) A therapeutic in Claim 1, which is an GCG peptide encoded by a nucleic acid, such that Codon # 6 is TTT and / or Codon # 7 is GTT and / or Codon # 8 is GCT and / or Codon # 11 is TTT and / or Codon # 12 is GTC and / or Codon # 21 is AGA and / or Codon # 26 is ACT and / or Codon # 34 is TCT and / or Codon # 42 is TCT and / or Codon # 44 is CCT and / or Codon # 48 is AAT and / or Codon # 53 is CAT and / or Codon # 56 is GGA and / or Codon # 57 is ACT and / or Codon # 60 is TCT and / or Codon # 62 is TAT and / or Codon # 74 is TTT and / or Codon # 75 is GTC and / or Codon # 84 is AAT and / or Codon # 87 is AAT and / or Codon # 88 is ATT and / or Codon # 92 is CAT and / or Codon # 93 is GAT and / or Codon # 95 is TTT and / or Codon # 98 is CAT and / or Codon # 99 is GCT and / or Codon # 105 is TCT and / or Codon # 115 is GCT and / or Codon # 119 is TTT and / or Codon # 120 is ATT and / or Codon # 133 is CCT and / or Codon # 136 is GTT and / or Codon # 137 is GCT and / or Codon # 138 is ATT and / or Codon # 146 is CAT and / or Codon # 147 is GCT and / or Codon # 148 is GAT and / or Codon # 153 is GAT and / or Codon # 163 is GCT . 73) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT . 74) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 10 is TATand / or Codon # 11 is TCA and / or Codon # 18 is GCA and / or Codon # 20 is GCA and / or Codon # 21 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 29 is GGA and / or Codon # 31 is CCA and / or Codon # 32 is AGT and / or Codon # 33 is TCA and / or Codon # 34 is GGA and / or Codon # 35 is GCA and / or Codon # 36 is CCA and / or Codon # 37 is CCA and / or Codon # 38 is CCA and / or Codon # 39 is TCA . 75) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 32 is TCG . 76) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 20 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 32 is TCC and / or Codon # 33 is TCT and / or Codon # 34 is GGA . 77) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT and / or Codon # 8 is AGC and / or Codon # 10 is TAT and / or Codon # 20 is GCT . 78) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT and / or Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 20 is GCT and / or Codon # 21 is GCT . 79) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 10 is TAT and / or Codon # 12 is ATA . 80) A therapeutic in Claim 1, which is an GGG peptide encoded by a nucleic acid, such that Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 12 is ATA and / or Codon # 20 is GCT and / or Codon # 29 is GGA and / or Codon # 33 is TCT and / or Codon # 34 is GGA . 81) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 7 is TTT and / or Codon # 29 is TCA and / or Codon # 51 is CGG and / or Codon # 55 is GGA and / or Codon # 61 is TAT and / or Codon # 62 is TCA and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 91 is ATA and / or Codon # 94 is AGA and / or Codon # 97 is CGG and / or Codon # 129 is CTC and / or Codon # 138 is CTC . 82) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 4 is ACT and / or Codon # 6 is ACT and / or Codon #7 is TTT and / or Codon # 8 is GCA and / or Codon # 13 is TCA and / or Codon # 17 is GCA and / or Codon # 21 is GGG and / or Codon # 29 is TCA and / or Codon # 30 is GCA and / or Codon # 32 is CCA and / or Codon # 33 is TCA and / or Codon # 35 is CCA and / or Codon # 38 is TCA and / or Codon # 39 is CAT and / or Codon # 40 is GCA and / or Codon # 43 is TCA and / or Codon # 44 is TCA and / or Codon # 45 is CCT and / or Codon # 47 is CCT and / or Codon # 48 is AGA and / or Codon # 50 is CCA and / or Codon # 51 is AGA and / or Codon # 52 is TAT and / or Codon # 53 is GCA and / or Codon # 55 is GGA and / or Codon # 56 is ACT and / or Codon # 59 is TCA and / or Codon # 61 is TAT and / or Codon # 62 is TCA and / or Codon # 63 is ATT and / or Codon # 64 is GCT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 79 is GCT and / or Codon # 85 is AAT and / or Codon # 89 is CAT and / or Codon # 90 is AAT and / or Codon # 91 is ATT and / or Codon # 92 is ACT and / or Codon # 94 is AGA and / or Codon # 96 is GCA and / or Codon # 97 is AGA and / or Codon # 98 is GCA and / or Codon # 102 is GCA and / or Codon # 103 is TCA and / or Codon # 105 is GCA and / or Codon # 107 is AGA and / or Codon # 112 is GCA and / or Codon # 115 is CCT and / or Codon # 117 is TCA and / or Codon # 118 is TCA and / or Codon # 119 is CCA and / or Codon # 120 is GCA and / or Codon # 123 is CCA and / or Codon # 124 is TCA and / or Codon # 125 is GAT and / or Codon # 129 is CTC and / or Codon # 130 is AGA and / or Codon # 139 is GCA and / or Codon # 145 is ACT and / or Codon # 149 is AGA and / or Codon # 151 is AGA and / or Codon # 152 is TCA and / or Codon # 153 is AGA . 83) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 17 is GCA and / or Codon # 27 is CAC and / or Codon # 29 is AGC and / or Codon # 39 is CAT and / or Codon # 45 is CCT and / or Codon # 50 is CCT and / or Codon # 55 is GGA and / or Codon # 57 is TTT and / or Codon # 59 is AGC and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 107 is CGC and / or Codon # 112 is GCA . 84) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 3 is GCA and / or Codon # 7 is TTT and / or Codon # 17 is GCT and / or Codon # 18 is GTT and / or Codon # 21 is GGG and / or Codon # 27 is CAC and / or Codon # 29 is TCT and / or Codon # 39 is CAT and / or Codon # 45 is CCT and / or Codon # 50 is CCT and / or Codon # 51 is AGA and / or Codon # 55 is GGA and / or Codon # 57 is TTT and / or Codon # 59 is TCT and / or Codon # 62 is TCT and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 74 is GTC and / or Codon # 85 is AAT and / or Codon # 89is CAT and / or Codon # 107 is AGA and / or Codon # 112 is GCA and / or Codon # 124 is TCT and / or Codon # 130 is AGA and / or Codon # 151 is AGA and / or Codon # 153 is AGA . 85) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 16 is CTT and / or Codon # 17 is GCA and / or Codon # 20 is CTT and / or Codon # 36 is GTA and / or Codon # 47 is CCT and / or Codon # 53 is GCT and / or Codon # 61 is TAT and / or Codon # 89 is CAT and / or Codon # 112 is GCA and / or Codon # 130 is CGC and / or Codon # 146 is AAC . 86) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 16 is CTT and / or Codon # 17 is GCA and / or Codon # 20 is CTT and / or Codon # 29 is TCT and / or Codon # 34 is CTA and / or Codon # 36 is GTT and / or Codon # 47 is CCT and / or Codon # 48 is AGA and / or Codon # 52 is TAT and / or Codon # 53 is GCT and / or Codon # 59 is TCT and / or Codon # 61 is TAT and / or Codon # 63 is ATT and / or Codon # 73 is TTT and / or Codon # 79 is GCT and / or Codon # 85 is AAT and / or Codon # 89 is CAT and / or Codon # 96 is GCA and / or Codon # 97 is AGA and / or Codon # 107 is AGA and / or Codon # 112 is GCT and / or Codon # 113 is GTT and / or Codon # 124 is TCT and / or Codon # 130 is AGA and / or Codon # 138 is TTG and / or Codon # 146 is AAC and / or Codon # 153 is AGA . 87) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 19 is GGG and / or Codon # 34 is CTA and / or Codon # 35 is CCT and / or Codon # 53 is GCT and / or Codon # 61 is TAT and / or Codon # 74 is GTC and / or Codon # 85 is AAC and / or Codon # 86 is GAT and / or Codon # 89 is CAT and / or Codon # 115 is CCT . 88) A therapeutic in Claim 1, which is an GIP peptide encoded by a nucleic acid, such that Codon # 19 is GGG and / or Codon # 20 is TTG and / or Codon # 21 is GGG and / or Codon # 29 is TCT and / or Codon # 34 is CTA and / or Codon # 35 is CCT and / or Codon # 52 is TAT and / or Codon # 53 is GCT and / or Codon # 59 is TCT and / or Codon # 61 is TAT and / or Codon # 62 is TCT and / or Codon # 63 is ATT and / or Codon # 74 is GTC and / or Codon # 89 is CAT and / or Codon # 115 is CCT and / or Codon # 124 is TCT . 89) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 2 is ATA and / or Codon # 12 is ATA and / or Codon # 33 is GTT and / or Codon # 40 is CAT and / or Codon # 47 is AAT and / or Codon # 48 is AGT and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / orCodon # 65 is TTT and / or Codon # 66 is AGG and / or Codon # 70 is GGA and / or Codon # 72 is TTT and / or Codon # 76 is GTC and / or Codon # 77 is TCA and / or Codon # 104 is AGT and / or Codon # 107 is GGA and / or Codon # 110 is CCA and / or Codon # 129 is GGA and / or Codon # 132 is CCT . 90) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 2 is ATA and / or Codon # 3 is CCA and / or Codon # 4 is GCA and / or Codon # 8 is GCA and / or Codon # 12 is ATT and / or Codon # 13 is GTC and / or Codon # 16 is GCA and / or Codon # 21 is ACT and / or Codon # 23 is TCA and / or Codon # 24 is GAT and / or Codon # 27 is TCA and / or Codon # 31 is AGA and / or Codon # 32 is TCA and / or Codon # 33 is GTT and / or Codon # 34 is TCA and / or Codon # 40 is CAT and / or Codon # 47 is AAT and / or Codon # 48 is AGT and / or Codon # 51 is AGA and / or Codon # 56 is AGA and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 65 is TTT and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 70 is GGA and / or Codon # 71 is ACT and / or Codon # 72 is TTT and / or Codon # 73 is ACT and / or Codon # 74 is TCA and / or Codon # 75 is GAT and / or Codon # 77 is TCA and / or Codon # 78 is TCA and / or Codon # 84 is GCA and / or Codon # 85 is GCA and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 90 is GCA and / or Codon # 94 is GAT and / or Codon # 96 is AGA and / or Codon # 101 is CCT and / or Codon # 102 is AGA and / or Codon # 104 is TCA and / or Codon # 105 is AGA and / or Codon # 106 is AAT and / or Codon # 108 is CCA and / or Codon # 109 is GGT and / or Codon # 110 is CCA and / or Codon # 113 is GGA and / or Codon # 115 is AGA and / or Codon # 116 is AGA and / or Codon # 119 is AGA and / or Codon # 120 is AGA and / or Codon # 122 is AGA and / or Codon # 123 is CCT and / or Codon # 124 is AGA and / or Codon # 126 is TCA and / or Codon # 129 is GGA and / or Codon # 130 is CCT and / or Codon # 132 is CCT . 91) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 32 is TCC and / or Codon # 40 is CAT and / or Codon # 51 is CGC and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 66 is AGG and / or Codon # 75 is GAT and / or Codon # 104 is TCA and / or Codon # 107 is GGT . 92) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 23 is TCA and / or Codon # 24 is GAT and / or Codon # 27 is AGT and / or Codon # 28 is GTC and / or Codon # 31 isAGG and / or Codon # 32 is AGT and / or Codon # 33 is GTC and / or Codon # 34 is TCT and / or Codon # 40 is CAT and / or Codon # 51 is AGA and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 84 is GCT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 104 is TCA and / or Codon # 105 is AGG and / or Codon # 106 is AAT and / or Codon # 113 is GGA and / or Codon # 120 is AGA . 93) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 28 is GTG and / or Codon # 60 is CAA and / or Codon # 66 is AGG and / or Codon # 74 is TCA and / or Codon # 92 is TTG and / or Codon # 96 is CGC and / or Codon # 101 is CCG and / or Codon # 106 is AAC and / or Codon # 113 is GGA and / or Codon # 119 is CGC and / or Codon # 127 is CAT and / or Codon # 132 is CCT . 94) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 4 is GCA and / or Codon # 12 is ATA and / or Codon # 27 is TCT and / or Codon # 28 is GTC and / or Codon # 31 is AGA and / or Codon # 32 is TCT and / or Codon # 33 is GTT and / or Codon # 60 is CAA and / or Codon # 66 is AGA and / or Codon # 67 is CAT and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 92 is TTG and / or Codon # 96 is AGA and / or Codon # 98 is TTG and / or Codon # 102 is AGA and / or Codon # 108 is CCA and / or Codon # 113 is GGA and / or Codon # 116 is AGA and / or Codon # 119 is AGA and / or Codon # 120 is AGA and / or Codon # 127 is CAT and / or Codon # 132 is CCT . 95) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 3 is CCT and / or Codon # 12 is ATA and / or Codon # 27 is TCC and / or Codon # 32 is TCC and / or Codon # 40 is CAT and / or Codon # 60 is CAA and / or Codon # 61 is GAT and / or Codon # 63 is CAT and / or Codon # 75 is GAT and / or Codon # 93 is GTC and / or Codon # 106 is AAC and / or Codon # 107 is GGT . 96) A therapeutic in Claim 1, which is an GLP-1, Apelin, PTHY peptide encoded by a nucleic acid, such that Codon # 3 is CCT and / or Codon # 12 is ATT and / or Codon # 13 is GTC and / or Codon # 23 is TCT and / or Codon # 24 is GAT and / or Codon # 27 is AGT and / or Codon # 28 is GTC and / or Codon # 32 is AGT and / or Codon # 33 is GTC and / or Codon # 34 is TCT and / or Codon # 40 is CAT and / or Codon # 60 is CAA and / or Codon# 61 is GAT and / or Codon # 63 is CAT and / or Codon # 67 is CAT and / or Codon # 68 is GGA and / or Codon # 74 is TCT and / or Codon # 75 is GAT and / or Codon # 84 is GCT and / or Codon # 88 is TTT and / or Codon # 89 is ATT and / or Codon # 94 is GAT and / or Codon # 108 is CCT and / or Codon # 113 is GGA and / or Codon # 120 is AGA . 97) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 18 is CTC and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 40 is TTT and / or Codon # 57 is ACT and / or Codon # 76 is AGT and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 98 is ACC and / or Codon # 99 is AGT and / or Codon # 108 is GGT and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 137 is TCA and / or Codon # 156 is CCA and / or Codon # 162 is GCT and / or Codon # 165 is CTT and / or Codon # 174 is CTT and / or Codon # 188 is GTC and / or Codon # 195 is TCT and / or Codon # 205 is CCA and / or Codon # 208 is CGG and / or Codon # 212 is GGA and / or Codon # 214 is TTT and / or Codon # 218 is GTC and / or Codon # 219 is TCA and / or Codon # 246 is AGT and / or Codon # 249 is GGA and / or Codon # 252 is CCA and / or Codon # 271 is GGA and / or Codon # 274 is CCT . 98) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCA and / or Codon # 4 is GAT and / or Codon # 6 is ACT and / or Codon # 7 is GGG and / or Codon # 8 is TTT and / or Codon # 11 is TCA and / or Codon # 16 is TCA and / or Codon # 19 is GCA and / or Codon # 24 is GGA and / or Codon # 25 is GCA and / or Codon # 28 is GCT and / or Codon # 29 is CAT and / or Codon # 30 is CCA and / or Codon # 32 is CCA and / or Codon # 34 is TCA and / or Codon # 35 is TCA and / or Codon # 36 is CCA and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 51 is ACT and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 57 is ACT and / or Codon # 59 is GCA and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 68 is ACT and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCA and / or Codon # 73 is GCA and / or Codon # 76 is TCA and / or Codon # 77 is CCA and / or Codon # 79 is TCA and / or Codon # 85 is GCA and / or Codon # 88 is CCA and / or Codon # 89 is GGA and / or Codon# 95 is GGA and / or Codon # 98 is ACT and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 105 is AGA and / or Codon # 106 is CCA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 111 is TAT and / or Codon # 113 is TCA and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCA and / or Codon # 121 is TGT and / or Codon # 122 is AGT and / or Codon # 124 is AGA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 137 is TCA and / or Codon # 139 is GCA and / or Codon # 140 is CAT and / or Codon # 143 is CCA and / or Codon # 147 is CCA and / or Codon # 151 is TCA and / or Codon # 152 is CCA and / or Codon # 153 is CAT and / or Codon # 154 is AGA and / or Codon # 156 is CCA and / or Codon # 157 is GCA and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 161 is CCA and / or Codon # 162 is GCA and / or Codon # 163 is AGA and / or Codon # 165 is CTT and / or Codon # 166 is CCA and / or Codon # 168 is CCA and / or Codon # 171 is CCA and / or Codon # 172 is CCA and / or Codon # 173 is GCA and / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 177 is CCA and / or Codon # 178 is CCA and / or Codon # 182 is GCA and / or Codon # 183 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 190 is TCA and / or Codon # 191 is TCA and / or Codon # 193 is CCA and / or Codon # 194 is CTA and / or Codon # 195 is AGT and / or Codon # 199 is CCA and / or Codon # 200 is TCA and / or Codon # 203 is AGA and / or Codon # 204 is TCA and / or Codon # 205 is CCA and / or Codon # 206 is TCA and / or Codon # 208 is AGG and / or Codon # 209 is CAT and / or Codon # 210 is GGA and / or Codon # 212 is GGA and / or Codon # 213 is ACT and / or Codon # 214 is TTT and / or Codon # 215 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 219 is TCA and / or Codon # 220 is TCA and / or Codon # 226 is GCA and / or Codon # 227 is GCA and / or Codon # 230 is TTT and / or Codon # 231 is ATT and / or Codon # 232 is GCA and / or Codon # 236 is GAT and / or Codon # 238 is AGA and / or Codon # 243 is CCT and / or Codon # 244 is AGA and / or Codon # 246 is TCA and / or Codon # 247 is AGA and / or Codon # 248 is AAT and / or Codon # 250 is CCA and / or Codon # 251 is GGT and / or Codon # 252 is CCA and / or Codon # 255 is GGA and / or Codon # 257 is AGA and / or Codon # 258 is AGA and / or Codon # 261 is AGA and / or Codon # 262 is AGA and / or Codon # 264 is AGA and / or Codon # 265 is CCT and / or Codon # 266 isAGA and / or Codon # 268 is TCA and / or Codon # 271 is GGA and / or Codon # 272 is CCT and / or Codon # 274 is CCT . 99) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is AGC and / or Codon # 6 is ACA and / or Codon # 15 is GTC and / or Codon # 16 is TCC and / or Codon # 40 is TTT and / or Codon # 54 is GCT and / or Codon # 60 is CAC and / or Codon # 69 is GTT and / or Codon # 76 is TCG and / or Codon # 77 is CCT and / or Codon # 89 is GGA and / or Codon # 101 is TTC and / or Codon # 109 is GCC and / or Codon # 115 is CAC and / or Codon # 123 is TTC and / or Codon # 128 is TTG and / or Codon # 132 is TAT and / or Codon # 133 is AAC and / or Codon # 139 is GCG and / or Codon # 156 is CCT and / or Codon # 158 is CCT and / or Codon # 162 is GCT and / or Codon # 167 is TTG and / or Codon # 168 is CCT and / or Codon # 183 is CCT and / or Codon # 185 is CCG and / or Codon # 186 is CCT and / or Codon # 187 is GAT and / or Codon # 188 is GTT and / or Codon # 190 is TCT and / or Codon # 212 is GGA and / or Codon # 213 is ACT and / or Codon # 217 is GAT and / or Codon # 246 is TCA and / or Codon # 248 is AAC and / or Codon # 249 is GGT and / or Codon # 260 is TTC and / or Codon # 261 is CGT and / or Codon # 272 is CCT . 100) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 6 is ACA and / or Codon # 8 is TTT and / or Codon # 10 is CAC and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is AGT and / or Codon # 40 is TTT and / or Codon # 45 is AGA and / or Codon # 47 is AGA and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 54 is GCT and / or Codon # 60 is CAC and / or Codon # 69 is GTT and / or Codon # 71 is GGA and / or Codon # 73 is GCT and / or Codon # 77 is CCT and / or Codon # 89 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 107 is GAT and / or Codon # 108 is GGA and / or Codon # 109 is GCC and / or Codon # 115 is CAC and / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 128 is TTG and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 137 is TCT and / or Codon # 140 is CAT and / or Codon # 156 is CCT and / or Codon # 158 is CCT and / or Codon # 159 is AGA and / or Codon # 162 is GCT and / or Codon # 163 is AGA and / or Codon # 167 is TTG and / or Codon # 168 is CCT and / or Codon # 183 is CCT and / or Codon # 186 is CCT and / or Codon # 187 is GAT and / or Codon # 188 is GTT and / or Codon # 190 is TCT and / or Codon # 191 is TCA and / or Codon # 209 is CAT and / or Codon # 210 is GGA and / or Codon # 212 is GGA and / or Codon # 213 isACT and / or Codon # 217 is GAT and / or Codon # 230 is TTT and / or Codon # 231 is ATT and / or Codon # 246 is TCA and / or Codon # 247 is AGA and / or Codon # 260 is TTC and / or Codon # 261 is AGA and / or Codon # 262 is AGA and / or Codon # 272 is CCT . 101) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is AGC and / or Codon # 11 is TCT and / or Codon # 12 is GGC and / or Codon # 18 is CTC and / or Codon # 23 is TTG and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 44 is GTT and / or Codon # 57 is ACA and / or Codon # 61 is TTG and / or Codon # 63 is ATC and / or Codon # 64 is CGC and / or Codon # 69 is GTT and / or Codon # 73 is GCT and / or Codon # 85 is GCT and / or Codon # 90 is GTT and / or Codon # 94 is TTG and / or Codon # 99 is AGT and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 120 is GCA and / or Codon # 123 is TTC and / or Codon # 124 is CGC and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 134 is GTC and / or Codon # 146 is TTG and / or Codon # 153 is CAC and / or Codon # 166 is CCT and / or Codon # 174 is CTT and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 195 is AGT and / or Codon # 213 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 235 is GTT and / or Codon # 248 is AAC and / or Codon # 249 is GGT and / or Codon # 255 is GGA and / or Codon # 257 is CGG and / or Codon # 265 is CCT and / or Codon # 269 is CAT and / or Codon # 274 is CCT . 102) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 4 is GAT and / or Codon # 8 is TTT and / or Codon # 11 is TCT and / or Codon # 12 is GGC and / or Codon # 16 is TCT and / or Codon # 18 is TTG and / or Codon # 19 is GCA and / or Codon # 23 is TTG and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 44 is GTT and / or Codon # 45 is AGA and / or Codon # 52 is GAT and / or Codon # 53 is GAT and / or Codon # 57 is ACA and / or Codon # 61 is TTG and / or Codon # 63 is ATC and / or Codon # 64 is AGA and / or Codon # 66 is GAT and / or Codon # 69 is GTT and / or Codon # 73 is GCT and / or Codon # 85 is GCT and / or Codon # 90 is GTT and / or Codon # 94 is TTG and / or Codon # 95 is GGA and / or Codon # 99 is AGT and / or Codon # 100 is AGA and / or Codon # 108 is GGA and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 117 is GAT and / or Codon # 118 is CCA and / or Codon # 120 is GCAand / or Codon # 123 is TTC and / or Codon # 124 is AGA and / or Codon # 129 is GAA and / or Codon # 130 is GAT and / or Codon # 132 is TAT and / or Codon # 133 is AAT and / or Codon # 146 is TTG and / or Codon # 154 is AGA and / or Codon # 159 is AGA and / or Codon # 162 is GCA and / or Codon # 166 is CCT and / or Codon # 174 is CTT and / or Codon # 175 is CCA and / or Codon # 183 is CCT and / or Codon # 186 is CCA and / or Codon # 187 is GAT and / or Codon # 195 is AGT and / or Codon # 197 is GTT and / or Codon # 203 is AGA and / or Codon # 213 is ACT and / or Codon # 216 is TCA and / or Codon # 217 is GAT and / or Codon # 235 is GTT and / or Codon # 237 is GGA and / or Codon # 238 is AGA and / or Codon # 250 is CCT and / or Codon # 255 is GGA and / or Codon # 257 is AGA and / or Codon # 258 is AGA and / or Codon # 261 is AGA and / or Codon # 265 is CCT and / or Codon # 266 is AGA and / or Codon # 269 is CAT and / or Codon # 274 is CCT . 103) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 10 is CAT and / or Codon # 15 is GTC and / or Codon # 16 is TCC and / or Codon # 30 is CCT and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 48 is TAC and / or Codon # 60 is CAC and / or Codon # 68 is ACG and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 89 is GGA and / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 106 is CCT and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 134 is GTT and / or Codon # 147 is CCT and / or Codon # 156 is CCT and / or Codon # 161 is CCT and / or Codon # 178 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 217 is GAT and / or Codon # 230 is TTT and / or Codon # 237 is GGA and / or Codon # 249 is GGT . 104) A therapeutic in Claim 1, which is an GLP-1, FGF21, Apelin peptide encoded by a nucleic acid, such that Codon # 3 is TCT and / or Codon # 6 is ACA and / or Codon # 11 is TCT and / or Codon # 15 is GTC and / or Codon # 16 is AGT and / or Codon # 19 is GCT and / or Codon # 30 is CCT and / or Codon # 32 is CCT and / or Codon # 40 is TTT and / or Codon # 41 is GGA and / or Codon # 45 is AGA and / or Codon # 48 is TAC and / or Codon # 51 is ACT and / or Codon # 60 is CAC and / or Codon # 67 is GGA and / or Codon # 68 is ACA and / or Codon # 69 is GTT and / or Codon # 70 is GGA and / or Codon # 71 is GGA and / or Codon # 72 is GCT and / or Codon # 73 is GCT and / or Codon # 76 is TCA and / or Codon # 77 is CCT and / or Codon # 88 is CCT and / or Codon # 89 is GGAand / or Codon # 95 is GGA and / or Codon # 101 is TTC and / or Codon # 105 is AGA and / or Codon # 106 is CCT and / or Codon # 108 is GGA and / or Codon # 115 is CAC and / or Codon # 116 is TTT and / or Codon # 118 is CCT and / or Codon # 133 is AAT and / or Codon # 137 is TCT and / or Codon # 147 is CCT and / or Codon # 156 is CCT and / or Codon # 161 is CCT and / or Codon # 168 is CCT and / or Codon # 175 is CCT and / or Codon # 178 is CCT and / or Codon # 185 is CCA and / or Codon # 186 is CCT and / or Codon # 191 is TCT and / or Codon # 210 is GGA and / or Codon # 217 is GAT and / or Codon # 226 is GCT and / or Codon # 230 is TTT and / or Codon # 237 is GGA and / or Codon # 238 is AGA and / or Codon # 248 is AAT and / or Codon # 250 is CCT and / or Codon # 261 is AGA . 105) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is GTC and / or Codon # 11 is TCA . 106) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GCA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 11 is TCA and / or Codon # 12 is TCA and / or Codon # 18 is GCA and / or Codon # 19 is GCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 24 is GCA and / or Codon # 30 is AGA . 107) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 5 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT . 108) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GCT and / or Codon # 5 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 22 is TTT and / or Codon # 23 is ATT . 109) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT . 110) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 18 is GCA . 111) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT .112) A therapeutic in Claim 1, which is an GLP-1 peptide encoded by a nucleic acid, such that Codon # 2 is GCT and / or Codon # 8 is TCT and / or Codon # 18 is GCT and / or Codon # 22 is TTT and / or Codon # 23 is ATT . 113) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 12 is ATT and / or Codon # 17 is ATT . 114) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 10 is TAT and / or Codon # 11 is TCA and / or Codon # 12 is ATT and / or Codon # 17 is ATT and / or Codon # 18 is GCT and / or Codon # 22 is GCT and / or Codon # 23 is TTT and / or Codon # 24 is GTC and / or Codon # 28 is ATT and / or Codon # 29 is GCA and / or Codon # 30 is GGA and / or Codon # 32 is CCA and / or Codon # 33 is AGT and / or Codon # 34 is TCA and / or Codon # 35 is GGA and / or Codon # 36 is GCA and / or Codon # 37 is CCA and / or Codon # 38 is CCA and / or Codon # 39 is CCA and / or Codon # 40 is TCA . 115) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 11 is TCT and / or Codon # 24 is GTC . 116) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 8 is TCT and / or Codon # 11 is TCT and / or Codon # 24 is GTC and / or Codon # 28 is ATT and / or Codon # 29 is GCA and / or Codon # 30 is GGA and / or Codon # 34 is TCT and / or Codon # 35 is GGA . 117) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 11 is TCT and / or Codon # 22 is GCG and / or Codon # 33 is TCG and / or Codon # 38 is CCA . 118) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 11 is TCT and / or Codon # 17 is ATT and / or Codon # 23 is TTT and / or Codon # 24 is GTC and / or Codon # 27 is TTG and / or Codon # 28 is ATT and / or Codon # 29 is GCT and / or Codon # 33 is TCC and / or Codon # 34 is TCT and / or Codon # 35 is GGA and / or Codon # 38 is CCA and / or Codon # 39 is CCA .119) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 10 is TAT and / or Codon # 11 is TCT and / or Codon # 24 is GTC . 120) A therapeutic in Claim 1, which is an mGLP-1, GIP peptide encoded by a nucleic acid, such that Codon # 1 is TAT and / or Codon # 2 is GGA and / or Codon # 8 is TCT and / or Codon # 10 is TAT and / or Codon # 11 is TCT and / or Codon # 17 is ATT and / or Codon # 24 is GTC and / or Codon # 29 is GCT and / or Codon # 30 is GGA and / or Codon # 34 is TCT . 121) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 6 is TTT and / or Codon # 10 is GTC and / or Codon # 11 is TCA . 122) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GGA and / or Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 6 is TTT and / or Codon # 7 is ACT and / or Codon # 8 is TCA and / or Codon # 9 is GAT and / or Codon # 11 is TCA and / or Codon # 12 is TCA and / or Codon # 18 is GCA and / or Codon # 19 is GCA and / or Codon # 22 is TTT and / or Codon # 23 is ATT and / or Codon # 24 is GCA and / or Codon # 28 is GAT and / or Codon # 30 is AGA . 123) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 5 is ACT . 124) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 4 is GGA and / or Codon # 5 is ACT and / or Codon # 18 is GCT and / or Codon # 23 is ATT and / or Codon # 28 is GAT . 125) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT . 126) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 5 is ACT and / or Codon # 7 is ACT . 127) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 22 is TTT. 128) A therapeutic in Claim 1, which is an mGLP-1 peptide encoded by a nucleic acid, such that Codon # 1 is CAT and / or Codon # 2 is GGA and / or Codon # 8 is TCT and / or Codon # 18 is GCT and / or Codon # 22 is TTT.

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