Related Experiment Video
Updated: Feb 16, 2026

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Intracellular Delivery of Native Proteins Facilitated by Cell-Penetrating Poly(disulfide)s
Linghui Qian1, Jiaqi Fu1, Peiyan Yuan1
1Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
Abstract:
Intracellular delivery of therapeutic proteins is highly challenging and in most cases requires chemical or genetic modifications. Herein, two complementary approaches for endocytosis-independent delivery of proteins to live mammalian cells are reported. By using either a "glycan" tag naturally derived from glycosylated proteins or a "traceless" tag that could reversibly label native lysines on non-glycosylated proteins, followed by bioorthogonal conjugation with cell-penetrating poly(disulfide)s (CPDs), we achieved intracellular delivery of proteins (including antibodies and enzymes) which, upon spontaneous degradation of CPDs, led to successful release of their "native" functional forms with immediate bioavailability.
More Related Videos
10:26Biotinylated Cell-penetrating Peptides to Study Intracellular Protein-protein Interactions
Published on: December 20, 2017
10:30Delivery of Proteins, Peptides or Cell-impermeable Small Molecules into Live Cells by Incubation with the Endosomolytic Reagent dfTAT
Published on: September 2, 2015
Related Concept Videos
Overview of Protein Sorting and Transport
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
Cotranslational Protein Translocation
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Post-translational Translocation of Proteins to the RER
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Protein Transport into the Inner Mitochondrial Membrane
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Nuclear Protein Sorting
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...