Structure-rich Phylomer peptide libraries, derived from biodiverse genomes, are a source of new cell penetrating peptides (CPPs) able to deliver therapeutic macromolecule cargoes to the intracellular space, thus opening up the druggable landscape. Employing a novel genetic screen known as the ‘endosome escape trap’ rare Phylomer CPPs were isolated that were able to deliver 60nm phage nanoparticle cargoes to the cytoplasm. These new cell penetrating Phylomers known as ‘FPPs’ show no evidence of toxicity and can be targeted to particular cell types using receptor binding domains. A variety of functional assays have been used to determine the extent of delivery of peptide and protein cargoes to the cytoplasm or nucleus. One such assay, based on split GFP complementation, has shown Phylomer FPPs to be 37-160 times more efficient at cytoplasmic delivery than conventional CPPs such as TAT or R9. Phylomer FPPs have also been shown to effectively deliver a 90 amino acid MYC inhibitor in a mouse model of breast cancer. This new delivery approach is being applied in conjunction with Phylomer peptides targeting transcription factor oncoproteins such as cMyc, MycN and STAT5, for more efficient cell targeted intracellular delivery of protein conjugates of more than 50 kDa in size, and also for intracellular delivery of nucleic acids.