Elastin-like polypeptide fusion for precision design of protein-polymer conjugates with improved pharmacology

Abstract

In a recent online publication of Advanced Materials, Professor Weiping Gao from Tsinghua University, reports such a methodology, ELPfusion. For the first time, they have demonstrated C-terminal fusion of IFN-α to an elastin-like polypeptide (ELP) to form a well-defined IFN-ELP fusion protein that was long acting and highly potent for cancer therapy. IFN-ELP fusion protein can be easily produced in E. coli with high yield and rapidly purified by a facile chromatography-free purification protocol of inverse transition cycling (ITC). Notably, the IFN-ELP fusion protein had much higher activity retention (41.1%) than PEGylated IFN-α (7%) and Albinterferon (1%). Moreover, IFN-ELP fusion protein possessed a 27.7-fold longer circulating half-life (8.6 h) than IFN-α (0.3 h) and dozens of times more tumor accumulation than IFN-α. More interestingly, the fusion protein almost completely inhibited tumor growth without apparent toxicity, while IFN-α had little inhibition effect on tumor growth. These findings may pave the way for the treatment of cancer and potentially viral diseases with IFN-ELP fusion proteins.