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Updated: Jun 27, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Non-covalent delivery of proteins into mammalian cells
Aurore Loudet1, Junyan Han, Rola Barhoumi
1Department of Chemistry, Texas A & M University, Box 30012, College Station, TX 77841, USA.
Abstract:
Substances that mediate the import of proteins into cells, "carriers", have many potential applications. The most potentially useful carriers do not have to be covalently linked to their protein cargoes. However, a common problem with all carrier molecules is that they tend to deposit the cargo proteins into endosomes; diffuse distribution in the cytosol is the desired outcome. This paper describes the import of four different labeled (Alexa Fluor 488) proteins (avidin, recombinant streptavidin, bovine serum albumin, and beta-galactosidase), with the well-known non-covalent carrier called pep-1 (also known as Chariot), with R(8) (a molecule that is not widely appreciated to import protein cargoes via a non-covalent mode of action), and with a new molecule called azo-R(8). The data collected from fluorescence microscopy and flow cytometry indicate that all three non-covalent carriers can facilitate transport. At 37 degrees C, import into endocytic compartments dominates, but at 4 degrees C weak, diffuse fluorescence is observed in the cytosol, indicative of a favorable mode of action.
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