The inefficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential of many proteins. Previously, it has been demonstrated that superpositively charged proteins are efficiently endocytosed and can bring associated proteins and nucleic acids into cells. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. The present invention provides endosomal escape peptides that enhance endosomal escape and cytosolic delivery of proteins and other agents of interest. In one aspect, described herein are novel fusion proteins comprising endosomal escape peptides fused to proteins and other agents of interest for delivery to a cell. Also provided herein are methods and compounds useful in preparing the fusion proteins, as well as pharmaceutical compositions and uses of the fusion proteins.
