Zuris, J.A. et al. Nat. Biotechnol. doi:10.1038/nbt.3081 (30 October 2014).

Exogenous proteins introduced into cells can carry out a myriad of desirable functions, but they cannot penetrate mammalian cells without assistance. One way around this is to introduce the protein in DNA or mRNA form, an approach that is widely used but bears some risk. Zuris et al. focused on delivering the proteins directly using cationic liposomal reagents routinely used for nucleic acid delivery. They first had to create a uniform negative charge in the protein cargo by complexing the protein with polyanionic macromolecules and then with cationic lipids to facilitate cellular uptake. This strategy allowed them to deliver Cre recombinase and gene-editing nucleases into cells as well as the inner ear of a mouse. The proteins retained high activity and showed more specific targeting than enzymes delivered by DNA transfections.