Considerations in the Use of Codon Optimization for Recombinant Protein Expression.

Codon optimization is a gene engineering approach that is commonly used for enhancing recombinant protein expression. This approach is possible because (1) degeneracy of the genetic code enables most amino acids to be encoded by multiple codons and (2) different mRNAs encoding the same protein can vary dramatically in the amount of protein expressed. However, because codon optimization potentially disrupts overlapping information encoded in mRNA coding regions, protein structure and function may be altered. This chapter discusses the use of codon optimization for various applications in mammalian cells as well as potential consequences, so that informed decisions can be made on the appropriateness of using this approach in each case.

[1]  Stanley Fields,et al.  Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast , 2016, Cell.

[2]  D. Inzé,et al.  Translational control of eukaryotic gene expression , 2009, Critical reviews in biochemistry and molecular biology.

[3]  C. Ling,et al.  Structural insights into ribosome translocation , 2016, Wiley interdisciplinary reviews. RNA.

[4]  W. V. van Zyl,et al.  Expression and comparison of codon optimised Aspergillus tubingensis amylase variants in Saccharomyces cerevisiae , 2017, FEMS yeast research.

[5]  Tamir Tuller,et al.  Mean of the Typical Decoding Rates: A New Translation Efficiency Index Based on the Analysis of Ribosome Profiling Data , 2014, G3: Genes, Genomes, Genetics.

[6]  J. Sidney,et al.  Cellular immune response to cryptic epitopes during therapeutic gene transfer , 2009, Proceedings of the National Academy of Sciences.

[7]  Carl Kingsford,et al.  Accurate Recovery of Ribosome Positions Reveals Slow Translation of Wobble-Pairing Codons in Yeast , 2016, RECOMB.

[8]  C. Gustafsson,et al.  You're one in a googol: optimizing genes for protein expression , 2009, Journal of The Royal Society Interface.

[9]  A. Komar,et al.  Single synonymous mutation in factor IX alters protein properties and underlies haemophilia B , 2016, Journal of Medical Genetics.

[10]  B. V. Ayyar,et al.  Optimizing antibody expression: The nuts and bolts. , 2017, Methods.

[11]  Antonio J Giraldez,et al.  Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition , 2016, The EMBO journal.

[12]  G. Edelman,et al.  Ribosomal shunting mediated by a translational enhancer element that base pairs to 18S rRNA. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[13]  James A. Williams Improving DNA vaccine performance through vector design. , 2014, Current gene therapy.

[14]  Jie Fang,et al.  Synonymous Rare Arginine Codons and tRNA Abundance Affect Protein Production and Quality of TEV Protease Variant , 2014, PloS one.

[15]  Nuno A. Fonseca,et al.  High-resolution mapping of transcriptional dynamics across tissue development reveals a stable mRNA–tRNA interface , 2014, Genome research.

[16]  Z. Bebők,et al.  Decoding mechanisms by which silent codon changes influence protein biogenesis and function. , 2015, The international journal of biochemistry & cell biology.

[17]  Alan Villalobos,et al.  Gene Designer: a synthetic biology tool for constructing artificial DNA segments , 2006, BMC Bioinformatics.

[18]  M. Pema,et al.  Codon Optimization Leads to Functional Impairment of RD114-TR Envelope Glycoprotein , 2017, Molecular therapy. Methods & clinical development.

[19]  Eric Rivals,et al.  Ribo-seq enlightens codon usage bias , 2017, DNA research : an international journal for rapid publication of reports on genes and genomes.

[20]  V. Mauro,et al.  Determinants of Initiation Codon Selection during Translation in Mammalian Cells , 2010, PloS one.

[21]  Leszek Kotula,et al.  Evaluation of Foreign Gene Codon Optimization in Yeast: Expression of a Mouse IG Kappa Chain , 1991, Bio/Technology.

[22]  Mian Zhou,et al.  Codon usage is an important determinant of gene expression levels largely through its effects on transcription , 2016, Proceedings of the National Academy of Sciences.

[23]  N. Shastri,et al.  Presentation of out-of-frame peptide/MHC class I complexes by a novel translation initiation mechanism. , 1999, Immunity.

[24]  Z. Ignatova,et al.  Alteration of protein function by a silent polymorphism linked to tRNA abundance , 2017, PLoS biology.

[25]  R. Fåhraeus,et al.  The source of MHC class I presented peptides and its implications. , 2016, Current opinion in immunology.

[26]  S. Franco,et al.  Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness. , 2016, Trends in microbiology.

[27]  Patricia Deng,et al.  The evolution and adaptation of A-to-I RNA editing , 2017, PLoS genetics.

[28]  R. Kastelein,et al.  Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression , 1987, Molecular and cellular biology.

[29]  Christina B. McCarthy,et al.  Bicodon bias can determine the role of synonymous SNPs in human diseases , 2017, BMC Genomics.

[30]  Eric D. Kelsic,et al.  RNA Structural Determinants of Optimal Codons Revealed by MAGE-Seq. , 2016, Cell systems.

[31]  V. Mauro,et al.  A critical analysis of codon optimization in human therapeutics. , 2014, Trends in molecular medicine.

[32]  W. Noderer,et al.  Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons , 2017, Nucleic acids research.

[33]  A. Paul,et al.  Recoding of the Vesicular Stomatitis Virus L Gene by Computer-Aided Design Provides a Live, Attenuated Vaccine Candidate , 2015, mBio.

[34]  Scott Emrich,et al.  %MinMax: A versatile tool for calculating and comparing synonymous codon usage and its impact on protein folding , 2018, Protein science : a publication of the Protein Society.

[35]  A. Fire,et al.  Wobble base-pairing slows in vivo translation elongation in metazoans. , 2011, RNA.

[36]  Guanghua Xiao,et al.  Nonoptimal codon usage influences protein structure in intrinsically disordered regions , 2015, Molecular microbiology.

[37]  D. Walsh,et al.  A Cap-to-Tail Guide to mRNA Translation Strategies in Virus-Infected Cells. , 2016, Annual review of virology.

[38]  A. Firth Mapping overlapping functional elements embedded within the protein-coding regions of RNA viruses , 2014, Nucleic acids research.

[39]  R. Parker,et al.  The link between adjacent codon pairs and mRNA stability , 2017, BMC Genomics.

[40]  Sebastian M. Waszak,et al.  A Dual Program for Translation Regulation in Cellular Proliferation and Differentiation , 2014, Cell.

[41]  Randall L. Kincaid,et al.  Heterologous Protein Expression Is Enhanced by Harmonizing the Codon Usage Frequencies of the Target Gene with those of the Expression Host , 2008, PloS one.

[42]  Nicholas T. Ingolia,et al.  Differences in codon bias and GC content contribute to the balanced expression of TLR7 and TLR9 , 2016, Proceedings of the National Academy of Sciences.

[43]  Justin Gardin,et al.  Measurement of average decoding rates of the 61 sense codons in vivo , 2014, eLife.

[44]  Chen Yanover,et al.  Building better drugs: developing and regulating engineered therapeutic proteins. , 2013, Trends in pharmacological sciences.

[45]  L. Duret,et al.  Recombination, meiotic expression and human codon usage , 2017, eLife.

[46]  Yi Xiao,et al.  Computational evidence that fast translation speed can increase the probability of cotranslational protein folding , 2015, Scientific Reports.

[47]  K. Politi,et al.  De novo selection of oncogenes , 2013, Proceedings of the National Academy of Sciences.

[48]  Bianca M. Schmitt,et al.  Codon-Driven Translational Efficiency Is Stable across Diverse Mammalian Cell States , 2016, PLoS genetics.

[49]  F. Supek The Code of Silence: Widespread Associations Between Synonymous Codon Biases and Gene Function , 2015, Journal of Molecular Evolution.

[50]  W. Uckert,et al.  Codon Optimization of the Human Papillomavirus E7 Oncogene Induces a CD8+ T Cell Response to a Cryptic Epitope Not Harbored by Wild-Type E7 , 2015, PloS one.

[51]  G. Edelman,et al.  Ribosomal tethering and clustering as mechanisms for translation initiation , 2006, Proceedings of the National Academy of Sciences.

[52]  J. Frank,et al.  Structure of the Mammalian Ribosomal 43S Preinitiation Complex Bound to the Scanning Factor DHX29 , 2013, Cell.

[53]  Nathan Morris,et al.  Codon Optimality Is a Major Determinant of mRNA Stability , 2015, Cell.

[54]  Enhancing functional expression of heterologous proteins through random substitution of genetic codes in the 5' coding region. , 2015, Biotechnology and bioengineering.

[55]  Elena Alkalaeva,et al.  Reassigning stop codons via translation termination: How a few eukaryotes broke the dogma , 2017, BioEssays : news and reviews in molecular, cellular and developmental biology.

[56]  R. Fåhraeus,et al.  Whisper mutations: cryptic messages within the genetic code , 2016, Oncogene.

[57]  E. Goldman tRNA and the Human Genome , 2011 .

[58]  J. Boeke,et al.  GeneDesign: rapid, automated design of multikilobase synthetic genes. , 2006, Genome research.

[59]  Tamir Tuller,et al.  The effect of tRNA levels on decoding times of mRNA codons , 2014, Nucleic acids research.

[60]  M. Wagner,et al.  A novel expression and purification system for the production of enzymatic and biologically active human granzyme B. , 2011, Journal of immunological methods.

[61]  Matthew S. Sachs,et al.  Codon Usage Influences the Local Rate of Translation Elongation to Regulate Co-translational Protein Folding. , 2015, Molecular cell.

[62]  E. Gould,et al.  Attenuation of Tick-Borne Encephalitis Virus Using Large-Scale Random Codon Re-encoding , 2015, PLoS pathogens.

[63]  Terrence S. Furey,et al.  A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins , 2010, BMC Bioinformatics.

[64]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[65]  N. Shastri,et al.  Nowhere to hide: unconventional translation yields cryptic peptides for immune surveillance , 2016, Immunological reviews.