Modulation of replicative fitness by deoptimization of synonymous codons
AssigneeThe United States of America as represented by the Secretary of the Department of Health and Human Services, Centers for Disease Control and Prevention
InventorsOlen M. Kew, Cara C. Burns, Jing Shaw, Raymond Campagnoli, Jacqueline Quay
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Abstract
Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.
Claims29
A method of reducing replicative fitness of a virus, comprising:
- preparing a viral nucleic acid molecule comprising at least twenty deoptimized codons in a coding sequence of the virus by replacing each of the at least twenty codons in the coding sequence with a synonymous codon less frequently used in the virus, thereby generating a deoptimized viral nucleic acid molecule that reduces replicative fitness of the virus.
Dependencies are inferred from the claim text.