Journal of Vaccines & Vaccination

Codon harmonization, a step beyond optimization to capture the natural rhythm of protein translation

10^th Euro Global Summit and Expo on Vaccines & Vaccination

June 16-18, 2016 Rome, Italy

Bettina Werle, N Mariano, C Mignon, S Chenavas, G Stadthagen, A Lugari, C Perot, S Donnat, P Lagoutte F Diot and R Sodoyer

Bioaster, France
Cad4Bio, France

Scientific Tracks Abstracts: J Vaccines Vaccin

Abstract:

Today, a growing body of evidence demonstrates that synonymous codon usage is non random and can affect protein biogenesis. Moreover their direct effects on percentage of GC, alteration of the mRNA structure as well as the protein yield; functionality and misfolding have been demonstrated. The aim of this study is to compare algorithms for codon harmonization in order to optimize protein expression, protein yield and solubility in E. coli. In collaboration with Cad4Bio, a French bioinformatics company, the potential of novel algorithms was evaluated in comparison to common standard optimization and native sequences. One of these algorithms globally harmonizes synonymous codons in the original sequence in full respect of the codon usage table specific to the heterologous expression host. The second algorithm generates a recoded sequence in order to reproduce the native sequence CAI (Codon Adaptation Index) profile. Both algorithms were compared to native sequences and to a more classic codon optimization method used by gene providers. The productivity and solubility of three proteins of biomedical interest expressed in E. coli was used to evaluate the performance of all tested sequence optimization algorithms and screening platform. Selected proteins were bacterial, parasitic antigens and antibody fragment. Both algorithms global codon harmonization and CAI profile fitting lead to a significant increase in protein expression and solubility. We have demonstrated that synonymous codon usage can affect protein biogenesis and moreover influence the protein yield and solubility. Our data highlights the usefulness of specific algorithms for codon harmonization. These tools may participate as a solution provider of difficult to solubilizing proteins and antibody fragments.

Biography :

Bettina Werle has completed her PhD in Cellular and Molecular Biology and Biochemistry at University of Burgundy in 1998 in the field of recombinant vaccines for respiratory syncitial virus. She has joined INSERM U271 as a Postdoctoral fellow in 1999 working on rapid diagnostic tests on hepatitis B. She has later joined Merial as a Manager of Virology Lab at Bioresearch Merial In-Charge of Technology Platform for new recombinant vaccines in 2004. In 2009, she has joined Solvay as the Head of Genomic, Transcriptomic and Viral Vectors Platforms in Bourgundy. She has started working in Bioaster as a Manager of the unit protein and expression system engineering in 2013.

Email: bettina.werle@bioaster.org