Promoting Cell Fusion by Polyvalent DNA Ligands

Artificially induced in vitro cell fusion is one essential technique that has been extensively used for biological studies. Nevertheless, there is a lack of robust and efficient method to produce fused cells efficiently. Herein, we proposed to use cell-membrane-anchored polyvalent DNA ligands (PDL) to bring cells into close proximity by forming clusters to enhance PEG-induced cell fusion. PDL of complementary sequences are separately anchored onto different population of cells through cholesterol-induced hydrophobic insertion into lipid membrane. Cells are clustered via mixing cells of complementary PDL prior to cell fusion. PDL exhibited strong stability on cell membrane, induced efficient cell clustering, and eventually achieved cell fusion efficiently in combination with PEG induction. We demonstrated homogeneous and heterogeneous cell fusion of high yield on various cell types. This report presented a programmable yet robust technique for achieving efficient cell fusion that hold great application potentials.