Commentary
Skipping the co-expression problem: the new 2A "CHYSEL" technology
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Correspondence: Pablo de Felipe pdf@st-andrews.ac.uk
Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St. Andrews, North Haugh, St. Andrews KY16 9ST, Scotland, UK
Genetic Vaccines and Therapy 2004, 2:13 doi:10.1186/1479-0556-2-13
Published: 13 September 2004Abstract
The rapid progress in the field of genomics is increasing our knowledge of multi-gene diseases. However, any realistic hope of gene therapy treatment for those diseases needs first to address the problem of co-ordinately co-expressing several transgenes. Currently, the use of internal ribosomal entry sites (IRESs) is the strategy chosen by many researchers to ensure co-expression. The large sizes of the IRESs (~0.5 kb), and the difficulties of ensuring a well-balanced co-expression, have prompted several researchers to imitate a co-expression strategy used by many viruses: to express several proteins as a polyprotein. A small peptide of 18 amino acids (2A) from the foot-and-mouth disease virus (FMDV) is being used to avoid the need of proteinases to process the polyprotein. FMDV 2A is introduced as a linker between two proteins to allow autonomous intra-ribosomal self-processing of polyproteins. Recent reports have shown that this sequence is compatible with different sub-cellular targeting signals and can be used to co-express up to four proteins from a single retroviral vector. This short peptide provides a tool to allow the co-expression of multiple proteins from a single vector, a useful technology for those working with heteromultimeric proteins, biochemical pathways or combined/synergistic phenomena.