The National Institutes of Health (NIH) has awarded a Small Business Innovation Research (SBIR) grant to Ventria Bioscience and the University of Southern California (USC), with the goal of developing a cost-effective method for producing clinical-grade proinsulin-transferrin (ProINS-Tf) using Ventria Bioscience's ExpressTec recombinant expression system. ProINS-Tf is a fusion protein between proinsulin and transferrin and has been shown to exhibit enhanced, sustained, hypoglycemic efficacy in vivo compared to therapeutic insulin, making it a novel candidate treatment for diabetes.

The project is designed to achieve the following objectives: develop ExpressTec rice plants that make ProINS-Tf; screen for, select and expand the highest-yielding plants; purify recombinant ProINS-Tf; and confirm the biological activities of ProINS-Tf.

"Research has suggested that recombinant fusion proteins linking human transferrin to therapeutic proteins like proinsulin could act as liver-targeted prodrugs, with the potential to improve therapeutic efficacy and reduce systemic adverse effects," said Dr Wei-Chiang Shen, the John A Biles Professor in Pharmaceutical Sciences at the USC School of Pharmacy and the senior investigator for the project at USC. "However, therapeutic use of proinsulin-transferrin is currently economically unfeasible due to low yields and high costs associated with its production in mammalian cell lines. Successful completion of our objectives will represent an important first step in the development of a novel, cost-effective, hepatocyte-targeted prodrug candidate for the treatment of diabetes."

Diabetes is the largest and fastest-growing chronic, disabling and deadly disease affecting young and old people worldwide. Recombinant insulin is a standard therapy for diabetes management, but it faces multiple challenges including short in vivo pharmaceutical life, adverse metabolic effects and high cost of production. There is an urgent need to develop novel, inexpensive hypoglycemic agents to treat and arrest the rapid spread of this debilitating disease.

"It is worth noting that the importance of this study's results are not limited to diabetes research but will also translate to other therapeutic areas," said Dr Ning Huang, vice president of Research and Development at Ventria Bioscience. "The outcome of this study will serve as a proof of principle that biopharmaceutical-grade, recombinant human transferrin fusion proteins can be produced in a cost-effective manner for clinical development."

Dr Shen and his group have previously collaborated with Ventria Bioscience on the study of recombinant human transferrin. A recent paper published by the team in BMC Biotechnology demonstrated that Ventria Bioscience's Optiferrin (recombinant human transferrin) is functionally comparable to purified human transferrin in its ability to bind to the transferrin receptor (TFR) and participate in TFR-mediated endocytosis, intracellular iron delivery and processing in a variety of cultured mammalian and human cell lines.

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