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Virus attenuation by genome-scale changes in codon pair bias.


ABSTRACT: As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific "codon pair bias" provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid-independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This "death by a thousand cuts" strategy could be generally applicable to attenuating many kinds of viruses.

SUBMITTER: Coleman JR 

PROVIDER: S-EPMC2754401 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Virus attenuation by genome-scale changes in codon pair bias.

Coleman J Robert JR   Papamichail Dimitris D   Skiena Steven S   Futcher Bruce B   Wimmer Eckard E   Mueller Steffen S  

Science (New York, N.Y.) 20080601 5884


As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific "codon pair bias" provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of pr  ...[more]

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