Polypeptide and microprotein drugs have gradually become the research hotspots in the field of biopharmaceuticals due to high specificity and low toxicity. However, the stability of polypeptide and microprotein drugs in vivo and their capability to penetrate cell membrane are limited, which significantly constrains their clinical application. To resolve these challenges, Professor He Wangxiao's team from XJTU employed bionic protein design and response strategy to develop drugs with higher efficiency and better stability by imitating the self-assembly mechanism of proteins and peptides in nature.
In their first work, the team designed a transdermal prion-bionics supermolecule RSIprion to improve facial rejuvenation. This study reveals that abnormal interaction between SNAP25 and RAB3A proteins in facial nerve under tension state leads to the formation of dynamic skin wrinkles. RSIprion inhibits the abnormally high SNAP25-RAB3A interaction in facial nerve cells by imitating the internalization of prion particles into nerve cells, thereby reducing wrinkles around eyes and nose.
Relevant work has been published as an article entitled “A Transitional Prion-Bionics Supermolecule as a RAB3A Antagonist for Enhancing Facial Youthfulness" in Advance Science. Professor He Wangxiao from Xi'an Jiaotong University (XJTU) is the corresponding author. Professor Liu Wenjia from XJTU is the first and corresponding author of this article.
In their second work, the team developed an innovative inhibitor WntSI for the Wnt/β-catenin signaling pathway, and verified its application in overcoming drug resistance of EGFR-TKI non-small cell lung cancer (NSCLC) caused by MET amplification. This study found that in NSCLC, the amplification of MET will lead to abnormal positive feedback activation of the Wnt/β-catenin signaling pathway, thus promoting tumor progression and triggering drug resistance to EGFR-TKI. By designing a Wnt inhibitor specifically released in tumor cells with over-expression of MET, the team successfully suppressed the Wnt signaling pathway and significantly enhanced therapeutic effect. In preclinical models, WntSI shows superior biological safety and therapeutic potential, which brings new therapeutic hope for NSCLC drug-resistant patients.
These outcomes have been published as an article entitled "Reversing Met-Mediated Resistance in Oncogene-Driven NSCLC by Met-Activated Wnt" in Advance Science. Professor He Wangxiao from XJTU is the corresponding author. PhD Liu Na from Department of Oncology of the First Affiliated Hospital of XJTU is the first author.
