Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec
AbstractProinsulin-transferrin fusion protein (ProINS-Tf) has been designed and successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf). It was found that HEK-ProINS-Tf could be converted into an activated form in the liver. Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin analogue with liver-specific insulin action in streptozotocin (STZ)-induced type 1 diabetic mice. However, due to the low production yield from transfected HEK293 cells, there are other interesting features, including the oral bioavailability, which have not been fully explored and characterized. To improve the protein production yield, an alternative protein expression system, ExpressTec using transgenic rice (Oryza sativa L.), was used. The intact and active rice-derived ProINS-Tf (ExpressTec-ProINS-Tf) was successfully expressed from the transgenic rice expression system. Our results suggested that, although the insulin-like bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of in vivo blood glucose control was considerably stronger than that of HEK-ProINS-Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged control of blood glucose to near-normal levels after oral administration of ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is a promising insulin analog with advantages including low cost, prolonged and liver targeting effects, and most importantly, oral bioactivity. View Full-Text
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Chen, Y.-S.; Zaro, J.L.; Zhang, D.; Huang, N.; Simon, A.; Shen, W.-C. Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec. Int. J. Mol. Sci. 2018, 19, 378.
Chen Y-S, Zaro JL, Zhang D, Huang N, Simon A, Shen W-C. Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec. International Journal of Molecular Sciences. 2018; 19(2):378.Chicago/Turabian Style
Chen, Yu-Sheng; Zaro, Jennica L.; Zhang, Deshui; Huang, Ning; Simon, Andrew; Shen, Wei-Chiang. 2018. "Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec." Int. J. Mol. Sci. 19, no. 2: 378.
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