Modulation of replicative fitness by deoptimization of synonymous codons
AssigneeThe Government of the USA as represented by the Secretary of the Dept. of Health and Human Service
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 method of attenuating a bacterium, comprising preparing a bacterial nucleic acid molecule comprising at least twenty deoptimized codons in a coding sequence of the bacterium by replacing each of the at least twenty codons in the coding sequence with a synonymous codon less frequently used in the bacterium, thereby generating an attenuated bacterium comprising a deoptimized bacterial nucleic acid molecule.
Dependencies are inferred from the claim text.