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Updated: Apr 25, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Promises and pitfalls of intracellular delivery of proteins
Ailing Fu1, Rui Tang, Joseph Hardie
1Department of Chemistry, University of Massachusetts , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
Abstract:
The direct delivery of functional proteins into the cell cytosol is a key issue for protein therapy, with many current strategies resulting in endosomal entrapment. Protein delivery to the cytosol is challenging due to the high molecular weight and the polarity of therapeutic proteins. Here we review strategies for the delivery of proteins into cells, including cell-penetrating peptides, virus-like particles, supercharged proteins, nanocarriers, polymers, and nanoparticle-stabilized nanocapsules. The advantages and disadvantages of these approaches including cytosolar delivery are compared and contrasted, with promising pathways forward identified.
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