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 coexpressed within the same cell in order to assemble multimeric complexes, transfer biochemical pathways and 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 controls its protein biogenesis led to the discovery of a short oligopeptide sequence, ‘2A’, that is able to mediate a cotranslational 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 coexpression within the same cell. These sequences are now being used in the treatment of cancer, in the production of pluripotent stem cells, and to create transgenic plants and animals among a host of other biotechnological and biomedical applications.