Protein delivery into live cells by incubation with an endosomolytic agent

A Erazo-Oliveras, K Najjar, L Dayani, TY Wang… - Nature …, 2014 - nature.com
A Erazo-Oliveras, K Najjar, L Dayani, TY Wang, GA Johnson, JP Pellois
Nature methods, 2014nature.com
We report that a tetramethylrhodamine-labeled dimer of the cell-penetrating peptide TAT,
dfTAT, penetrates live cells by escaping from endosomes with high efficiency. By mediating
endosomal leakage, dfTAT also delivers proteins into cultured cells after a simple co-
incubation procedure. We achieved cytosolic delivery in several cell lines and primary cells
and observed that only a relatively small amount of material remained trapped inside
endosomes. Delivery did not require a binding interaction between dfTAT and a protein …
Abstract
We report that a tetramethylrhodamine-labeled dimer of the cell-penetrating peptide TAT, dfTAT, penetrates live cells by escaping from endosomes with high efficiency. By mediating endosomal leakage, dfTAT also delivers proteins into cultured cells after a simple co-incubation procedure. We achieved cytosolic delivery in several cell lines and primary cells and observed that only a relatively small amount of material remained trapped inside endosomes. Delivery did not require a binding interaction between dfTAT and a protein, multiple molecules could be delivered simultaneously, and delivery could be repeated. dfTAT-mediated delivery did not noticeably affect cell viability, cell proliferation or gene expression. dfTAT-based intracellular delivery should be useful for cell-based assays, cellular imaging applications and the ex vivo manipulation of cells.
nature.com