Codon Optimization in the Production of Recombinant Biotherapeutics: Potential Risks and Considerations.

Authors:

BioDrugs 2018 Feb;32(1):69-81

The Scripps Research Institute, La Jolla, CA, 92037, USA.

Biotherapeutics are increasingly becoming the mainstay in the treatment of a variety of human conditions, particularly in oncology and hematology. The production of therapeutic antibodies, cytokines, and fusion proteins have markedly accelerated these fields over the past decade and are probably the major contributor to improved patient outcomes. Today, most protein therapeutics are expressed as recombinant proteins in mammalian cell lines. An expression technology commonly used to increase protein levels involves codon optimization. This approach is possible because degeneracy of the genetic code enables most amino acids to be encoded by more than one synonymous codon and because codon usage can have a pronounced influence on levels of protein expression. Indeed, codon optimization has been reported to increase protein expression by >  1000-fold. The primary tactic of codon optimization is to increase the rate of translation elongation by overcoming limitations associated with species-specific differences in codon usage and transfer RNA (tRNA) abundance. However, in mammalian cells, assumptions underlying codon optimization appear to be poorly supported or unfounded. Moreover, because not all synonymous codon mutations are neutral, codon optimization can lead to alterations in protein conformation and function. This review discusses codon optimization for therapeutic protein production in mammalian cells.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40259-018-0261-xDOI Listing
February 2018
8 Reads

Publication Analysis

Top Keywords

codon optimization
28
codon
11
protein expression
8
increase protein
8
synonymous codon
8
codon usage
8
mammalian cells
8
protein
6
optimization
6
enables amino
4
assumptions underlying
4
optimization approach
4
cells assumptions
4
genetic code
4
involves codon
4
degeneracy genetic
4
code enables
4
approach degeneracy
4
protein levels
4
appear supported
4

References

(Supplied by CrossRef)

MR Ladisch et al.
Biotechnol Prog. 1992

K Lieuw et al.
J Blood Med. 2017

DC Andersen et al.
Curr Opin Biotechnol 2002

J Dumont et al.
Crit Rev Biotechnol 2016

HA Lagasse et al.
F1000Res 2017

JY Kim et al.
Appl Microbiol Biotechnol 2012

F Davami et al.
Avicenna J Med Biotechnol. 2014

L Delafosse et al.
J Biotechnol 2016

C Lattenmayer et al.
Biotechnol Bioeng 2007

O Kramer et al.
Appl Microbiol Biotechnol 2010

RG Harrison et al.
Proc Soc Exptl Biol Med. 1907

Similar Publications