US 2018/0008689 A1Published application

Rna virus attenuation by alteration of mutational robustness and sequence space

AssigneeInstitut Pasteur

InventorsMarco VIGNUZZI, Cyril BARBEZANGE, Moratorio GONZALO

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Abstract

The application generally relates to the attenuation of a RNA virus or of a clone thereof and involves the alteration of sequence space, more particularly the reduction, of mutational robustness of said RNA virus or clone. The means of the application are more particularly dedicated to the attenuation of an infectious RNA virus or clone, for the production of immunogenic composition or vaccine. More particularly, the means of the application involve the replacement of codon(s) by different codon(s), which is(are) selected to differ by only one nucleotide from a codon STOP, more particularly by different but synonymous codon(s), which is(are) selected to differ by only one nucleotide from a codon STOP.

Claims18

Dependent claims

A process of production of an attenuated RNA virus or of an attenuated cDNA clone thereof, by attenuation of an infectious RNA virus or of an infectious cDNA clone thereof, wherein said infectious RNA virus or infectious cDNA clone thereof comprises a RNA-dependent RNA polymerase, wherein said process comprises providing an infectious RNA virus or an infectious cDNA clone thereof, wherein said infectious cDNA clone comprises the cDNA sequence, which is the retrotranscript of the CDS of the genome of said RNA virus,

modifying the RNA genome of said infectious RNA virus or the retro-transcribed cDNA sequence of said cDNA clone, respectively,
wherein said modification comprises replacing at least one codon, which codes for Leu, Ser, Arg or Gly in said infectious RNA virus or infectious cDNA clone, by a different but synonymous codon,
wherein said different but synonymous codon is a codon, which differs by only one nucleotide from a STOP codon.

Dependencies are inferred from the claim text.