The Art of Gene Redesign and Recombinant Protein Production: Approaches and Perspectives

Chapter
Part of the Topics in Medicinal Chemistry book series (TMC, volume 21)

Abstract

In recent years, the demand for recombinant proteins for use in research laboratories or in medical settings has increased dramatically. Although a wide variety of recombinant protein expression systems and gene redesign approaches are available, obtaining active, correctly folded recombinant proteins in sufficient amounts remains a challenge in many cases. One of the main approaches to gene redesign with the potential to increase protein production involves introduction of synonymous codon substitutions in mRNAs aimed at increasing the rate/efficiency of translation. However, a number of recent studies have shown that synonymous codon substitutions can also negatively impact mRNA biogenesis, mRNA decoding, as well as protein folding and function. Maximizing the speed and output of translation may put conflicting demands on the protein synthesis machinery resulting in reduced accuracy of the decoding process and/or improper protein folding. An improved understanding of the impact of synonymous codon substitutions on mRNA/protein biogenesis and function is critically important for the development of safer and more effective recombinant protein therapeutics. This review discusses the most common approaches to gene redesign that involve synonymous codon substitutions and provides recommendations for their optimal use in light of recent developments in the field regarding the impact of synonymous codon usage on various aspects of protein production and function.

Keywords

Codon usage Gene redesign Mistranslation mRNA turnover Protein folding Protein synthesis Rare synonymous codons Recombinant protein therapeutics Synonymous codons 

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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Center for Gene Regulation in Health and Disease and Department of Biological, Geological and Environmental SciencesCleveland State UniversityClevelandUSA
  2. 2.DAPCEL, Inc.ClevelandUSA

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