Delivery of macromolecules into mammalian cells in vitro and in vivo has enabled new areas of research and offers the potential for powerful new treatment options. Recent research has generated many delivery platforms but these solutions remain limited by scope, potency and safety. We have reported a superpositively charged green fluorescent protein (+36 GFP) with the ability to deliver nucleic acids into a variety of mammalian cell lines in vitro and to potently deliver protein in vitro and in vivo without toxicity. These results have directed us to identify a subset of naturally occurring human proteins with similar but previously unknown cell-penetrating and protein delivery properties. Preliminary efforts have been made towards establishing the therapeutic potential for supercharged proteins replacement of the cytosolic enzyme, argininosuccinate synthase. Preliminary efforts have also been made towards enhancing endosomal escape with \(His_{39} GFP\).