RNA Sequence Optimizations for Efficient Heterologous Protein Expression: A Pipeline Using a Genetic Algorithm and a Simulated Annealing Approach

Résumé

In the context of vaccine development, it is common to consider different strategies, including that of attempting to express certain sub-parts of the virus made up of proteins in a heterologous cellular host. The latter is generally chosen for its ease of maintenance in cell culture, which is the case of the E coli bacterium. But transposing a coding sequence from one organism to another is far from trivial and several problems can occur such as the choice of different synonymous codons, the introduction of alternative ribosome binding sites, or a secondary structure of the messenger RNA preventing ribosome pairing. All these elements can lead to the synthesis of a non-functional protein. The present work proposes a sequence design solution using a pipeline of different modules to satisfy different constraints when transposing the expression of a protein from an original host to a heterologous host. Due to the complexity and the number of possibilities, a manual search is not feasible, nor is an exhaustive computer search. Other strategies such as a genetic algorithm or simulated annealing must be considered to try to obtain an optimal solution satisfying the different constraints in a reasonable time.

la date de réponse	23 juin 2023
langue originale	Anglais
L'institution diplômante	Universite de Namur
Superviseur	Jean-Marie Jacquet (Promoteur)