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Updated: May 30, 2025

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Strategies and challenges of cytosolic delivery of proteins
Yuanyuan Li1, Baojie Du2, Lichao Yu1
1School of Life Science and Technology, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Abstract:
The cytosolic delivery of therapeutic proteins represents a promising strategy for addressing diseases caused by protein dysfunction. Despite significant advances, efficient delivery remains challenging due to barriers such as cell membrane impermeability, endosomal sequestration and protein instability. This review summarises recent progress in protein delivery systems, including physical, chemical and biological approaches, with a particular focus on strategies that enhance endosomal escape and targeting specificity. We further discuss the clinical translatability of these approaches and propose future directions for improving delivery efficiency and safety, ultimately unlocking the therapeutic potential of intracellular proteins.
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