Genome Synthesis Technique for Virus Vaccine Development

A group at Stony Brook University has modified the polio virus to create a weakened version, which, when injected, went on to effectively immunize lab mice. The team of molecular biologists and computer scientists used a novel algorithm to sort through potential recordings of the genome that would produce the desired proteins. The technique may lead to practical, systematic methods of developing future viral vaccines.

Because of the redundancy of the genetic code, there are an unimaginably large number of ways to encode any given protein. For poliovirus proteins, there are more possible encodings (10 to the 442 power) than atoms in the universe. Using a powerful computer algorithm, the team found particular re-codings of the genome predicted to weaken the virus.
The researchers made hundreds of small mutations in the genome that perfectly preserved the viral proteins but changed the way those proteins were encoded by RNA (ribonucleic acid), so that pairs of amino acids were added by transfer RNAs (tRNAs) that rarely work together in normal proteins. They call the process “Synthetic Attenuated Virus Engineering,” or “SAVE.” The resulting virus contains completely authentic, wild-type poliovirus proteins. However, each of the hundreds of mutations causes a tiny defect by creating an obstacle – a genetic “speed bump” – in translating the genetic code into a protein.
“Translation of this unusual genome into viral proteins was inefficient, and the most highly re-coded virus was weakened to the point where it was unable to infect cells,” says J. Robert Coleman, Lead Author and a graduate student in Molecular Genetics and Microbiology.
The reduced translational efficiency of these chimeric viruses reduced their ability to cause disease. The team injected mice with the re-coded polioviruses. Most mice showed no signs of disease but did produce anti-polio antibodies. These mice were then immune against infection by the normal, fully virulent poliovirus.

Press release: SBU Team Designs Customized “Wimpy” Polioviruses, A Method That Could Be A New Path To Vaccines …
Abstract in Science: Virus Attenuation by Genome-Scale Changes in Codon Pair Bias
Image: The structural appearance of Poliovirus (type I, Mahoney strain) coating protein