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.

The present disclosure relates to recombinant RNA molecules encoding an oncolytic virus genome. The present disclosure further relates to the encapsulation of the recombinant RNA molecules and the use of the recombinant RNA molecules and/or particles for the treatment and prevention of cancer.

The disclosure provides a recombinant oncolytic virus, a synthetic DNA sequence and applications of the virus. The recombinant oncolytic virus includes a genome and an exogenous DNA sequence inserted in the genome. The exogenous DNA sequence adapts to express a basic peptide fragment, to increase the environmental pH in a host infected by the recombinant oncolytic virus. The basic peptide fragment includes more than 60% of basic amino acids. The recombinant oncolytic virus and the synthetic DNA sequence of the disclosure are used to prepare an anti-tumor drug.