Attenuated virus mutated at sites of evolutionarily conserved RNA structure
AssigneesRamot at Tel-Aviv University Ltd., Yeda Research and Development Co. Ltd., Synvaccine Ltd.
InventorsTamir Tuller, Eli Goz, Shimshi Atar, Hadas Zur
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Abstract
Attenuated viruses and methods of designing them are disclosed. In one embodiment, there is disclosed an attenuated form of a virulent virus comprising an RNA encoding a viral protein or a nucleic acid sequence transcribable to said RNA, wherein the folding energy or structure of the RNA is changed at positions of evolutionarily conserved RNA structures with respect to that of said RNA encoding said viral protein in the virulent virus so as to bring about attenuation of the virus.
Claims18
An attenuated form of a virulent virus comprising an RNA encoding a viral protein or a nucleic acid sequence transcribable to said RNA, comprising at least one nucleotide in a region of evolutionarily conserved local RNA folding energy synonymously substituted to another nucleotide,
- wherein said region of evolutionarily conserved local RNA folding energy comprises folding energy below a predetermined threshold and said substitution increases said folding energy, or
- said region of evolutionarily conserved RNA folding energy comprises folding energy above a predetermined threshold and said substitution decreases said folding energy, wherein said predetermined threshold is derived from the average local folding energy of a randomized sequence of the virulent virus, wherein said randomized sequence encodes an amino acid sequence which is identical to the amino acid sequence of said virulent virus;
- and wherein said viral protein of said attenuated virus comprises an amino acid sequence which is identical to the amino acid sequence of said viral protein of the virulent virus and said at least one substitution decreases replicative fitness of said attenuated form of a virus as compared to said virulent virus.
Dependencies are inferred from the claim text.