Modular protein engineering for non-viral gene therapy.

Despite the recognized potential of viral vectors for gene therapy, growing biological concerns are prompting the exploration of safer, non-viral vectors to deliver therapeutic nucleic acids. In this context, recombinant proteins can be bioproduced on a large scale, without the need for further in vitro modifications, being free of known or suspected biohazards. For these vehicles to act as efficient gene-delivery devices, they must perform relevant functions that mimic those of viruses; namely, nucleic acid condensation, targeted cell attachment and internalization, endosomal escape and nuclear transfer. Modular engineering enables the construction of chimeric polypeptides in which selected domains, potentially from different origins, provide the required activities. An equilibrate combination and spatial distribution of such partner elements has generated promising prototypes, able to deliver expressible DNA to tissue culture but also to specific cell-types in whole organisms.