Oligonucleotide-Based Mimetics of Hepatocyte Growth Factor

Oligonucleotide‐based hepatocyte growth factor (HGF) mimetics are described. A DNA aptamer to Met, a cognate receptor for HGF, was shown to induce Met activation when used in dimer form. The most potent aptamer dimer, ss‐0, which was composed solely of 100‐mer single‐stranded DNA, exhibited nanomolar potency. Aptamer ss‐0 reproduced HGF‐induced cellular behaviors, including migration and proliferation. The present work sheds light on oligonucleotides as a novel chemical entity for the design of growth factor mimetics. Bridging the gap: A 100‐mer ssDNA was developed as a potent hepatocyte growth factor (HGF) mimetic. This ssDNA was designed to induce receptor dimerization at the cell surface and subsequent signal transduction in the same way as the natural growth factor. This new class of synthetic ligands reproduced growth factor induced cellular behaviors, including cell migration and proliferation.