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Science. 2008 Jun 27;320(5884):1784-7. doi: 10.1126/science.1155761.

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

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  • 1Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.


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.

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