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DI 04/31

Modulating mutational frequency to optimize protein evolution

Inventor: Didier MAZEL and Guillaume CAMBRAY

Description of invention:

The genetic code is used by all organisms across the animal and plant kingdoms to specify protein sequence. An inherent feature of the triplet code is its redundancy, i.e. multiple DNA sequences can encode the same amino acid sequence. Each organism exhibits a characteristic codon bias, a usage preference for different synonymous codons. Each polynucleotide sequence occupies a ?sequence space? which reflects the coding potential resulting from single point mutations.

Researchers at the Pasteur Institute have developed a method for modulating the ability of a gene to mutate. By analyzing the codon usage and carefully selecting a synonymous nucleotide sequence, one can engineer genes with a higher, lower or different capacity to mutate. This allows for the widening and optimization of the evolutionary landscape of a given polynucleotide sequence. The researchers have developed a computer-implemented methodology (Evolutionary Landscape Painter) for analyzing synonymous nucleic acid sequences and comparing their mutational capacity. Engineered gene sequences with an enhanced capacity to mutate can be used to select functional protein variants. Conversely, decreasing the mutational capacity can render genes more stable and less vulnerable to undesired changes.

Specific advantages:

Computer-implemented methodology to explore the ?sequence space’ occupied by a polynucleotide sequence.
Engineering of genetic elements with enhanced mutational capacity to optimize protein evolution and the selection of functional variants.
Engineering decreased mutational capacity of a genetic element to render it more stable and resistant to mutational inactivation.

Potential applications :

Useful tool to control polynucleotide evolution and to enhance functional selective screening.
To explore, for a given polynucleotide sequence, an evolutionary landscape not otherwise available.
To generate genetic material with improved resistance to the effects of mutation.

Patent status:

United States provisional patent application filed 17 September 2004
Software protected

Relevant publications:

Manuscript in preparation


Contact : Christophe Poquet, Business Development Manager - Office of Technology Transfer
 Institut Pasteur - 28 Rue du Docteur Roux - 75724 Paris Cedex 15 FRANCE
Tel : 33.1.40 61 33 97 - Fax : 33.1.40.61.37.32 - email : cpoquet@pasteur.fr