A critical analysis of codon optimization in human therapeutics

Trends in Molecular Medicine

Volumn 20, Issue 11, 2014, Pages 604-613

  Mauro, Vincent P ^a   Chappell, Stephen A ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

A to I editing; Codon optimization; Gene therapy; MRNA therapy; TRNA wobble; Vaccine

Indexed keywords

MESSENGER RNA; NUCLEIC ACID; TRANSFER RNA; CODON; PEPTIDE; RECOMBINANT PROTEIN;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; BASE PAIRING; CLINICAL EFFECTIVENESS; CODON; CODON OPTIMIZATION; CODON USAGE; GENE SEQUENCE; GENE SYNTHESIS; GENETIC CODE; GENETIC ENGINEERING; HISTORY OF MEDICINE; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; MEDICAL CARE; NONHUMAN; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN POLYMORPHISM; PROTEIN SECONDARY STRUCTURE; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REVIEW; RIBOSOME; RNA EDITING; RNA SEQUENCE; SAFETY; TRANSLATION INITIATION; ANIMAL; CHEMISTRY; GENE EXPRESSION REGULATION; GENE THERAPY; GENETICS; METABOLISM; PROCEDURES; PROTEIN ENGINEERING;

ANIMALS; CODON; GENE EXPRESSION REGULATION; GENETIC ENGINEERING; GENETIC THERAPY; HUMANS; PEPTIDES; PROTEIN ENGINEERING; RECOMBINANT PROTEINS; RNA EDITING; RNA, MESSENGER; RNA, TRANSFER;

EID: 84908701702     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2014.09.003     Document Type: Review

References (125)

1. Welch M., et al. You're one in a googol: optimizing genes for protein expression. J. R. Soc. Interface 2009, 6(Suppl. 4):S467-S476.
2. Kudla G., et al. Coding-sequence determinants of gene expression in Escherichia coli. Science 2009, 324:255-258.
3. Ward N.J., et al. Codon optimization of human factor VIII cDNAs leads to high-level expression. Blood 2011, 117:798-807.
4. Shabalina S.A., et al. Sounds of silence: synonymous nucleotides as a key to biological regulation and complexity. Nucleic Acids Res. 2013, 41:2073-2094.
5. Tsai C.J., et al. Synonymous mutations and ribosome stalling can lead to altered folding pathways and distinct minima. J. Mol. Biol. 2008, 383:281-291.
6. Agashe D., et al. Good codons, bad transcript: large reductions in gene expression and fitness arising from synonymous mutations in a key enzyme. Mol. Biol. Evol. 2013, 30:549-560.
7. Spencer P.S., et al. Silent substitutions predictably alter translation elongation rates and protein folding efficiencies. J. Mol. Biol. 2012, 422:328-335.
8. Zhou J.H., et al. The effects of the synonymous codon usage and tRNA abundance on protein folding of the 3C protease of foot-and-mouth disease virus. Infect. Genet. Evol. 2013, 16:270-274.
9. Zhang F., et al. Differential arginylation of actin isoforms is regulated by coding sequence-dependent degradation. Science 2010, 329:1534-1537.
10. Hunt R., et al. Silent (synonymous) SNPs: should we care about them?. Methods Mol. Biol. 2009, 578:23-39.
11. Katsnelson A. Breaking the silence. Nat. Med. 2011, 17:1536-1538.
12. Sauna Z.E., Kimchi-Sarfaty C. Understanding the contribution of synonymous mutations to human disease. Nat. Rev. Genet. 2011, 12:683-691.
13. Chen R., et al. Non-synonymous and synonymous coding SNPs show similar likelihood and effect size of human disease association. PLoS ONE 2010, 5:e13574.
14. Kimchi-Sarfaty C., et al. Building better drugs: developing and regulating engineered therapeutic proteins. Trends Pharmacol. Sci. 2013, 34:534-548.
15. US Food and Drug Administration Paving the Way for Personalized Medicine: FDA's Role in a New Era of Medical Product Development 2013, FDA.
16. Dittmar K.A., et al. Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2006, 2:e221.
17. Goldman E. tRNA and the Human Genome. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:16980-16985.
18. Murphy F.V.t., Ramakrishnan V. Structure of a purine-purine wobble base pair in the decoding center of the ribosome. Nat. Struct. Mol. Biol. 2004, 11:1251-1252.
19. Su A.A., Randau L. A-to-I and C-to-U editing within transfer RNAs. Biochemistry (Mosc). 2011, 76:932-937.
20. Agris P.F. Decoding the genome: a modified view. Nucleic Acids Res. 2004, 32:223-238.
21. Rogalski M., et al. Superwobbling facilitates translation with reduced tRNA sets. Nat. Struct. Mol. Biol. 2008, 15:192-198.
22. Alkatib S., et al. The contributions of wobbling and superwobbling to the reading of the genetic code. PLoS Genet. 2012, 8:e1003076.
23. Itakura K., et al. Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. Science 1977, 198:1056-1063.
24. Air G.M., et al. Gene F of bacteriophage phiX174. Correlation of nucleotide sequences from the DNA and amino acid sequences from the gene product. J. Mol. Biol. 1976, 107:445-458.
25. Efstratiadis A., et al. The primary structure of rabbit beta-globin mRNA as determined from cloned DNA. Cell 1977, 10:571-585.
26. Fiers W., et al. A-protein gene of bacteriophage MS2. Nature 1975, 256:273-278.
27. Post L.E., et al. Nucleotide sequence of the ribosomal protein gene cluster adjacent to the gene for RNA polymerase subunit beta in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 1979, 76:1697-1701.
28. Ikemura T. Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal for a synonymous codon choice that is optimal for the E. coli translational system. J. Mol. Biol. 1981, 151:389-409.
29. Bennetzen J.L., Hall B.D. Codon selection in yeast. J. Biol. Chem. 1982, 257:3026-3031.
30. Sharp P.M., et al. Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res. 1986, 14:5125-5143.
31. Richardson S.M., et al. GeneDesign: rapid, automated design of multikilobase synthetic genes. Genome Res. 2006, 16:550-556.
32. Villalobos A., et al. Gene Designer: a synthetic biology tool for constructing artificial DNA segments. BMC Bioinformatics 2006, 7:285.
33. Gao W., et al. UpGene: Application of a web-based DNA codon optimization algorithm. Biotechnol. Prog. 2004, 20:443-448.
34. Jayaraj S., et al. GeMS: an advanced software package for designing synthetic genes. Nucleic Acids Res. 2005, 33:3011-3016.
35. Wu G., et al. The Synthetic Gene Designer: a flexible web platform to explore sequence manipulation for heterologous expression. Protein Expr. Purif. 2006, 47:441-445.
36. Bode M., et al. TmPrime: fast, flexible oligonucleotide design software for gene synthesis. Nucleic Acids Res. 2009, 37:W214-W221.
37. Raab D., et al. The GeneOptimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization. Syst. Synth. Biol. 2010, 4:215-225.
38. Gaspar P., et al. EuGene: maximizing synthetic gene design for heterologous expression. Bioinformatics 2012, 28:2683-2684.
39. Angov E., et al. Heterologous protein expression is enhanced by harmonizing the codon usage frequencies of the target gene with those of the expression host. PLoS ONE 2008, 3:e2189.
40. Fuglsang A. Codon optimizer: a freeware tool for codon optimization. Protein Expr. Purif. 2003, 31:247-249.
41. Qian W., et al. Balanced codon usage optimizes eukaryotic translational efficiency. PLoS Genet. 2012, 8:e1002603.
42. Hatfield G.W., Roth D.A. Optimizing scaleup yield for protein production: Computationally Optimized DNA Assembly (CODA) and Translation Engineering. Biotechnol. Annu. Rev. 2007, 13:27-42.
43. Gustafsson C., et al. Engineering genes for predictable protein expression. Protein Expr. Purif. 2012, 83:37-46.
44. Curran J.F., Yarus M. Rates of aminoacyl-tRNA selection at 29 sense codons in vivo. J. Mol. Biol. 1989, 209:65-77.
45. Kurland C., Gallant J. Errors of heterologous protein expression. Curr. Opin. Biotechnol. 1996, 7:489-493.
46. Bonekamp F., et al. Translation rates of individual codons are not correlated with tRNA abundances or with frequencies of utilization in Escherichia coli. J. Bacteriol. 1989, 171:5812-5816.
47. Wu X., et al. Codon optimization reveals critical factors for high level expression of two rare codon genes in Escherichia coli: RNA stability and secondary structure but not tRNA abundance. Biochem. Biophys. Res. Commun. 2004, 313:89-96.
48. Rosano G.L., Ceccarelli E.A. Rare codon content affects the solubility of recombinant proteins in a codon bias-adjusted Escherichia coli strain. Microb. cell Fact. 2009, 8:41.
49. Hershey J.W., et al. Principles of translational control: an overview. Cold Spring Harb. Perspect. Biol. 2012, 4:a011528.
50. Komar A.A. A pause for thought along the co-translational folding pathway. Trends Biochem. Sci. 2009, 34:16-24.
51. Rosenblum G., et al. Quantifying elongation rhythm during full-length protein synthesis. Mol. Cell 2013, 135:11322-11329.
52. Cannarozzi G., et al. A role for codon order in translation dynamics. Cell 2010, 141:355-367.
53. Stadler M., Fire A. Wobble base-pairing slows in vivo translation elongation in metazoans. RNA 2011, 17:2063-2073.
54. Li G.W., et al. The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria. Nature 2012, 484:538-541.
55. Mauro V.P., Edelman G.M. The ribosome filter redux. Cell Cycle 2007, 6:2246-2251.
56. Dresios J., et al. An mRNA-rRNA base-pairing mechanism for translation initiation in eukaryotes. Nat. Struct. Mol. Biol. 2006, 13:30-34.
57. Chappell S.A., et al. Ribosomal shunting mediated by a translational enhancer element that base pairs to 18S rRNA. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:9488-9493.
58. Larsen B., et al. rRNA-mRNA base pairing stimulates a programmed -1 ribosomal frameshift. J. Bacteriol. 1994, 176:6842-6851.
59. Luttermann C., Meyers G. The importance of inter-and intramolecular base pairing for translation reinitiation on a eukaryotic bicistronic mRNA. Genes Dev. 2009, 23:331-344.
60. Hausser J., et al. Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation. Genome Res. 2013, 23:604-615.
61. Hu S., et al. Genetic code-guided protein synthesis and folding in E. coli. J. Biol. Chem. 2013, 288:30855-30861.
62. Sander I.M., et al. Expanding Anfinsen's principle: contributions of synonymous codon selection to rational protein design. J. Am. Chem. Soc. 2014, 136:858-861.
63. Hoekema A., et al. Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression. Mol. Cell. Biol. 1987, 7:2914-2924.
64. Kotula L., Curtis P.J. Evaluation of foreign gene codon optimization in yeast: expression of a mouse IG kappa chain. Biotechnology (N.Y.) 1991, 9:1386-1389.
65. Gustafsson C., et al. Codon bias and heterologous protein expression. Trends Biotechnol. 2004, 22:346-353.
66. Charneski C.A., Hurst L.D. Positively charged residues are the major determinants of ribosomal velocity. PLoS Biol. 2013, 11:e1001508.
67. Chen C., et al. Dynamics of translation by single ribosomes through mRNA secondary structures. Nat. Struct. Mol. Biol. 2013, 20:582-588.
68. Dana A., Tuller T. Determinants of translation elongation speed and ribosomal profiling biases in mouse embryonic stem cells. PLoS Comput. Biol. 2012, 8:e1002755.
69. Subramanian S. Nearly neutrality and the evolution of codon usage bias in eukaryotic genomes. Genetics 2008, 178:2429-2432.
70. Andersson S.G., Kurland C.G. Codon preferences in free-living microorganisms. Microbiol. Rev. 1990, 54:198-210.
71. Klumpp S., et al. On ribosome load, codon bias and protein abundance. PLoS ONE 2012, 7:e48542.
72. Larsen H.B. Kenyan dominance in distance running. Comp. Biochem. Physiol. A: Mol. Integr. Physiol. 2003, 136:161-170.
73. Matsuda D., Mauro V.P. Determinants of initiation codon selection during translation in mammalian cells. PLoS ONE 2010, 5:e15057.
74. Malarkannan S., et al. Presentation of out-of-frame peptide/MHC class I complexes by a novel translation initiation mechanism. Immunity 1999, 10:681-690.
75. Ingolia N.T., et al. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 2009, 324:218-223.
76. Ingolia N.T., et al. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 2011, 147:789-802.
77. Lee S., et al. Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:E2424-E2432.
78. Menschaert G., et al. Deep proteome coverage based on ribosome profiling aids MS-based protein and peptide discovery and provides evidence of alternative translation products and near-cognate translation initiation events. Mol. Cell. Proteomics 2013, 12:1780-1790.
79. Slavoff S.A., et al. Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat. Chem. Biol. 2013, 9:59-64.
80. Kozak M. Initiation of translation in prokaryotes and eukaryotes. Gene 1999, 234:187-208.
81. Chappell S.A., et al. Ribosomal tethering and clustering as mechanisms for translation initiation. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:18077-18082.
82. Irimia M., et al. Evolutionarily conserved A-to-I editing increases protein stability of the alternative splicing factor Nova1. RNA Biol. 2012, 9:12-21.
83. Godfried Sie C., et al. IGFBP7's susceptibility to proteolysis is altered by A-to-I RNA editing of its transcript. FEBS Lett. 2012, 586:2313-2317.
84. Ramaswami G., et al. Identifying RNA editing sites using RNA sequencing data alone. Nat. Methods 2013, 10:128-132.
85. Nishikura K. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 2010, 79:321-349.
86. Hideyama T., et al. Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons. Neurobiol. Dis. 2012, 45:1121-1128.
87. Silberberg G., et al. Deregulation of the A-to-I RNA editing mechanism in psychiatric disorders. Hum. Mol. Genet. 2012, 21:311-321.
88. Choudhury Y., et al. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells. J. Clin. Invest. 2012, 122:4059-4076.
89. Enstero M., et al. A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins. BMC Bioinformatics 2010, 11:6.
90. Fath S., et al. Multiparameter RNA and codon optimization: a standardized tool to assess and enhance autologous mammalian gene expression. PLoS ONE 2011, 6:e17596.
91. Lorimer D., et al. Gene composer: database software for protein construct design, codon engineering, and gene synthesis. BMC Biotechnol. 2009, 9:36.
92. Raghava G.P., Sahni G. GMAP: a multi-purpose computer program to aid synthetic gene design, cassette mutagenesis and the introduction of potential restriction sites into DNA sequences. Biotechniques 1994, 16:1116-1123.
93. Hoover D.M., Lubkowski J. DNAWorks: an automated method for designing oligonucleotides for PCR-based gene synthesis. Nucleic Acids Res. 2002, 30:e43.
94. Huang G., et al. An efficient and rapid method for cDNA cloning from difficult templates using codon optimization and SOE-PCR: with human RANK and TIMP2 gene as examples. Biotechnol. Lett. 2011, 33:1939-1947.
95. Li M.H., et al. De novo gene synthesis design using TmPrime software. Methods Mol. Biol. 2012, 852:225-234.
96. Kumar D., et al. Validation of RNAi silencing specificity using synthetic genes: salicylic acid-binding protein 2 is required for innate immunity in plants. Plant J. 2006, 45:863-868.
97. Liss M., et al. Embedding permanent watermarks in synthetic genes. PLoS ONE 2012, 7:e42465.
98. Satya R.V., et al. A pattern matching algorithm for codon optimization and CpG motif-engineering in DNA expression vectors. Proc. IEEE Comput. Soc. Bioinform. Conf. 2003, 2:294-305.
99. Harish N., et al. DyNAVacS: an integrative tool for optimized DNA vaccine design. Nucleic Acids Res. 2006, 34:W264-W266.
100. Sharp P.M., Li W.H. The codon adaptation index - a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987, 15:1281-1295.
101. Wright F. The 'effective number of codons' used in a gene. Gene 1990, 87:23-29.
102. Townsend A., et al. Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J. Exp. Med. 1988, 168:1211-1224.
103. Yewdell J.W., et al. Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class I molecules?. J. Immunol. 1996, 157:1823-1826.
104. Yewdell J.W., Nicchitta C.V. The DRiP hypothesis decennial: support, controversy, refinement and extension. Trends Immunol. 2006, 27:368-373.
105. Cardinaud S., et al. The synthesis of truncated polypeptides for immune surveillance and viral evasion. PLoS ONE 2010, 5:e8692.
106. Reits E.A., et al. The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 2000, 404:774-778.
107. Apcher S., et al. Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:11572-11577.
108. Apcher S., et al. Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:17951-17956.
109. Starck S.R., et al. Leucine-tRNA initiates at CUG start codons for protein synthesis and presentation by MHC class I. Science 2012, 336:1719-1723.
110. Ingolia N.T., et al. The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. Nat. protoc. 2012, 7:1534-1550.
111. Mallela A., Nishikura K. A-to-I editing of protein coding and noncoding RNAs. Crit. Rev. Biochem. Mol. Biol. 2012, 47:493-501.
112. Paul M.S., Bass B.L. Inosine exists in mRNA at tissue-specific levels and is most abundant in brain mRNA. EMBO J. 1998, 17:1120-1127.
113. Penn A.C., et al. Reciprocal regulation of A-to-I RNA editing and the vertebrate nervous system. Front. Neurosci. 2013, 7:61.
114. Rodriguez J., et al. Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila. Mol. Cell 2012, 47:27-37.
115. Rieder L.E., Reenan R.A. The intricate relationship between RNA structure, editing, and splicing. Semin. Cell Dev. Biol. 2012, 23:281-288.
116. Kozak M. How do eucaryotic ribosomes select initiation regions in messenger RNA?. Cell 1978, 15:1109-1123.
117. Negrutskii B.S., et al. Supramolecular organization of the mammalian translation system. Proc. Natl. Acad. Sci. U.S.A. 1994, 91:964-968.
118. Stapulionis R., et al. Efficient mammalian protein synthesis requires an intact F-actin system. J. Biol. Chem. 1997, 272:24980-24986.
119. Barhoom S., et al. Quantitative single cell monitoring of protein synthesis at subcellular resolution using fluorescently labeled tRNA. Nucleic Acids Res. 2011, 39:e129.
120. Pavon-Eternod M., et al. Vaccinia and influenza A viruses select rather than adjust tRNAs to optimize translation. Nucleic Acids Res. 2013, 41:1914-1921.
121. Hirschmann W.D., et al. Scp160p is required for translational efficiency of codon-optimized mRNAs in yeast. Nucleic Acids Res. 2014, 42:4043-4055.
122. Crick F.H. Codon-anticodon pairing: the wobble hypothesis. J. Mol. Biol. 1966, 19:548-555.
123. Agris P.F., et al. tRNA's wobble decoding of the genome: 40 years of modification. J. Mol. Biol. 2007, 366:1-13.
124. Sprinzl M., et al. Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res. 1998, 26:148-153.
125. Peabody D.S. Translation initiation at non-AUG triplets in mammalian cells. J. Biol. Chem. 1989, 264:5031-5035.