Noninvasive intracellular delivery of functional peptides and proteins.

In order to probe intracellular signaling based on interactions of thousands of proteins expressed in the living cell, new methods of noninvasive delivery of functional peptides and proteins to cells have been developed. These include cellular import of peptides and proteins based on the cell-membrane-permeable properties of the hydrophobic region of a signal peptide sequence. The prototypical cell-permeable SN50 peptide, which contains the nuclear localization signal sequence of NK-kappaB p50, has been applied in multiple cell types to block nuclear import of this and other transcription factors. Further developments, including site-specific ligation of bipartite import peptides and production of import-competent recombinant proteins, provide the means for easy and rapid delivery of peptides and proteins to a wide spectrum of cells in order to regulate intracellular pathways involved in adhesion, signaling and trafficking to the nucleus.