Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity.

Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity. Biomaterials. 2020 Jul 21;257:120250 Authors: Lee JY, Park T, Hong E, Amatya R, Park KA, Park YH, Min KA, Jin M, Lee S, Hwang S, Roh GS, Shin MC Abstract A common bottleneck challenge for many therapeutic proteins lies in their short plasma half-lives, which often makes the treatment far less compliant or even disables achieving sufficient therapeutic efficacy. To address this problem, we introduce a novel drug delivery strategy based on the genetic fusion of an albumin binding domain (ABD) and an anti-neonatal Fc receptor (FcRn) affibody (AFF) to therapeutic proteins. This ABD-AFF fusion strategy can provide a synergistic effect on extending the plasma residence time by, on one hand, preventing the rapid glomerular filtration via ABD-mediated albumin binding and, on the other hand, increasing the efficiency of FcRn-mediated recycling by AFF-mediated high-affinity binding to the FcRn. In this research, we explored the feasibility of applying the ABD-AFF fusion strategy to exendin-4 (EX), a clinically available anti-diabetic peptide possessing a short plasma half-life. The EX-ABD-AFF produced from the E. coli displayed a remarkably (241-fold) longer plasma half-life than the SUMO tagged-EX (SUMO-EX) (0.7 h) in mice. Furthermore, in high-fat diet (HFD)-fed obese mice model, the EX-ABD-A...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research