The protein coexpression problem in biotechnology and biomedicine : virus 2A and 2A-like sequences provide a solution
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Synthetic biology enables us to create genes virtually at will. Ensuring that multiple genes are efficiently co-expressed within the same cell – to assemble multimeric complexes, to transfer biochemical pathways, to transfer ‘traits’, is more problematic. Viruses such as picornaviruses accomplish exactly this task: they generate multiple, different, proteins from a single open reading frame. The study of how foot-and-mouth disease virus (FMDV) controls it’s protein biogenesis lead to the discovery of a short oligopeptide sequence, ‘2A’, that is able to mediate a co-translational ‘cleavage’ between proteins. 2A and ‘2A-like’ sequences (from other viruses and cellular sequences) can be used to concatenate multiple gene sequences into a single gene, ensuring their co-expression within the same cell. These sequences are now being used in the treatment of cancer, in the production of pluripotent stem cells, to create transgenic plants and animals amongst a host of other biotechnological and biomedical applications.
Luke , G A & Ryan , M D 2013 , ' The protein coexpression problem in biotechnology and biomedicine : virus 2A and 2A-like sequences provide a solution ' Future Virology , vol 8 , no. 10 , pp. 983-996 . DOI: 10.2217/fvl.13.82
Copyright, Future Medicine Ltd.
The authors acknowledge the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC), the Wellcome Trust and the UK Medical Research Council (MRC).