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Int. J. Mol. Sci. 2018, 19(2), 378; https://doi.org/10.3390/ijms19020378

Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec

1
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA
2
Department of Pharmaceutical Sciences, West Coast University School of Pharmacy, Los Angeles, CA 90004, USA
3
Ventria Bioscience Inc., 2718 Industrial Drive, Junction City, KS 66441, USA
*
Author to whom correspondence should be addressed.
Received: 26 November 2017 / Revised: 23 January 2018 / Accepted: 24 January 2018 / Published: 26 January 2018
(This article belongs to the Special Issue Recombinant Proteins)
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Abstract

Proinsulin-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
Keywords: transgenic rice; proinsulin; transferrin; fusion protein; diabetes; oral delivery transgenic rice; proinsulin; transferrin; fusion protein; diabetes; oral delivery
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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.

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