Modulation of replicative fitness by deoptimization of synonymous codons
AssigneeThe Government of the United States of America as represented by the Secretary of the Department of Health and Human Services, Center for Disease Control and Prevention
InventorsOlen M. Kew, Cara Carthel 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.
Claims17
A modified respiratory syncytial virus (RSV) comprising:
- a fusion (F) or glycoprotein (G) coding sequence of the respiratory syncytial virus wherein at least twenty codons in the coding sequence are deoptimized as compared to its native coding sequence,
- wherein the at least twenty deoptimized codons are each a synonymous codon less frequently used in the native respiratory syncytial virus, wherein the synonymous codon less frequently used in the native respiratory syncytial virus is a codon that encodes the same amino acid, but the codon is an unpreferred codon by the native RSV for the amino acid.
Dependencies are inferred from the claim text.