A Bivalent Aptamer-Based DNA Agonist for EGFR Signaling Effectively Alleviates Ulcerative Colitis In Vivo

Area of Science:

• Biochemistry
• Molecular Biology
• Gastroenterology

Background:

• Epidermal growth factor (EGF) shows therapeutic potential for ulcerative diseases by activating epidermal growth factor receptor (EGFR) signaling.
• Current recombinant EGF proteins face limitations including poor stability and difficulty in modification, hindering clinical application.
• There is a critical need for novel EGFR agonists to treat ulcerative colitis effectively.

Purpose of the Study:

• To develop and characterize a novel DNA-based agonist for EGFR activation.
• To evaluate the efficacy of this DNA agonist in promoting cellular behaviors relevant to intestinal repair.
• To assess the therapeutic potential of the DNA agonist in an in vivo model of ulcerative colitis.

Main Methods:

• Design and synthesis of a bivalent aptamer DNA molecule (Dimer-YL) to induce EGFR dimerization.
• In vitro assessment of Dimer-YL's ability to promote cell proliferation, migration, and repair intercellular tight junctions.
• In vivo evaluation of Dimer-YL's therapeutic effects in a dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model.

Main Results:

• Dimer-YL successfully induced stable EGFR dimerization, recapitulating EGF-promoted cellular behaviors like proliferation and migration.
• The DNA agonist demonstrated efficacy in repairing damaged intercellular tight junctions.
• Dimer-YL significantly alleviated symptoms and pathology in a DSS-induced ulcerative colitis model.

Conclusions:

• Dimer-YL represents an innovative DNA molecule capable of effective EGFR activation through stable receptor dimerization.
• This DNA agonist offers a promising alternative to protein-based therapies for ulcerative colitis.
• The findings highlight Dimer-YL's potential as a therapeutic agent for EGFR-mediated diseases.