Work

Comparison of Receptor‐Mediated Endocytosis and Its Application to Enhance DNA Transfection by TFAMoplex

Year: 2026

Type: article

Abstract: Receptor‐targeting ligands can improve the specificity and cellular uptake of drugs and gene delivery systems. However, there is currently a lack of rapid, high‐throughput assays to identify ligands that efficiently induce endocytosis. To address this gap, we developed a flow cytometric assay that selectively quantifies internalized fluorescence, directly converting endosomal uptake into an easily measurable signal across entire cell populations and avoiding the ambiguity and labor intensity of microscopy‐based methods. Using this platform, we identified ligands that induce cellular uptake and applied them to the TFAMoplex, a modular, protein‐based nonviral gene delivery system recently developed in our group. Coupling of heparin‐binding epidermal growth factor, identified as an efficient internalizing ligand with the endocytosis assay, enhanced TFAMoplex uptake and transfection efficacy. These results support a generalizable strategy to rapidly screen uptake ligands, enabling the rational design of improved nonviral gene delivery systems.

Source: Advanced NanoBiomed Research

DOI: 10.1002/anbr.70124

Authors: David Scherer, Steffen Honrath, Jonas Kurmann, Alexander Klipp, Finn Brigger, Jean‐Christophe Leroux

Institutions: ETH Zurich, Institute of Pharmaceutical Sciences

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,940