A designer biomimetic vector with a chimeric architecture for targeted gene transfer

Designer biomimetic vectors are genetically engineered biomacromolecules that are designed to mimic viral characteristics in order to overcome the cellular barriers associated with the targeted gene transfer. The vector in this study was genetically engineered to contain at precise locations: a) four tandem repeating units of N-terminal domain of histone H2A to condense DNA into stable nanosize particles suitable for cellular uptake, b) a model targeting motif to target HER2 and enhance internalization of nanoparticles, and c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and promote escape of the nanoparticles into the cytosol. The results demonstrate that a fully functional, multi-domain, designer vector can be engineered to target cells with high specificity, overcome the biological barriers associated with targeted gene transfer, and mediate efficient gene transfer.

Graphical abstractSchematic representation of a designer biomimetic vector composed of a fusogenic peptide (FP), four repeating units of histone H2A (4HP), a cathepsin D substrate (CS), and a targeting motif (TM).Figure optionsDownload full-size imageDownload as PowerPoint slide