Internal ribosome entry site-based vectors for combined gene therapy

Figure 2 Internal ribosome entry site-based multicistronic vector concept. The internal ribosome entry site (IRES)-based expression cassette contains several genes, separated by IRESs, under the control of the same promoter (Pr). This transcription unit gives rise to a single mRNA coding the different genes. Translation initiation occurs at the 5’ end by the cap-dependent mechanism, resulting in translation of the first open reading frame (ORF, Gene A). Internal initiations of translation occur at each IRES, resulting in translation of the other ORFs (Genes B and C). Thus the multicistronic mRNA generates several proteins from a single transcription unit, allowing more stable long term expression and stable transgene ratio[9,48]. For each ORF, initiation (AUG) and termination (STOP) codons are indicated.