Intracellular Molecules Induced Extracellular Peptide Self‐Assembly for Efficient and Effective In Situ Cell Purification

Synthetic messenger RNA (mRNA) switches are powerful tools for in situ cell purification, especially for cells derived from stem cells. However, the retention effectiveness of the target cells is limited by the leaky expression of toxic protein. The elimination efficiency of non-target cells is also constrained due to the lack of signal amplification. In this study, we designed a novel approach that uses synthetic mRNA switch to convey intracellular marker molecule information into spatially controlled extracellular toxic assembly formation. The approach bypasses the use of toxic protein to ensure high target cell recovery effectiveness. Meanwhile, the marker molecule information is amplified at multiple levels to ensure high non-target cell elimination effectiveness. Our approach can be tailored to meet various in situ cell purification needs, promising high-quality in situ cell purification for a wide range of biomedical applications.