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Science 27 June 2008:
Vol. 320. no. 5884, pp. 1784 - 1787
DOI: 10.1126/science.1155761
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Reports

Virus Attenuation by Genome-Scale Changes in Codon Pair Bias

J. Robert Coleman,1 Dimitris Papamichail,2* Steven Skiena,2 Bruce Futcher,1 Eckard Wimmer,1{dagger} Steffen Mueller1

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.

1 Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794, USA.
2 Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA.

* Present address: Department of Computer Science, University of Miami, Coral Gables, FL 33124, USA.

{dagger} To whom correspondence should be addressed. E-mail: ewimmer{at}ms.cc.sunysb.edu

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