The protein coexpression problem in biotechnology and biomedicine : virus 2A and 2A-like sequences provide a solution

Abstract

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.