Full-length IgG antibodies that specifically bind to a target molecule with high affinity have been extensively developed as research tools, as well as for diagnostic and therapeutic purposes. However, these antibodies are designed primarily to target proteins expressed on the cell-surface or on some secreted proteins. This is because antibodies usually cannot cross intact cellular or subcellular membranes in living cells due to their large size and hydrophilicity. We have developed cell penetrating antibodies, which can access the cytosol of living cells following receptor-mediated endocytosis. This unique capability will allow these next-generation therapeutic antibodies to directly target cytosolic proteins associated with many human diseases that have been previously considered untreatable.