Programed Assembly of Nucleoprotein Nanoparticles Using DNA and Zinc Fingers for Targeted Protein Delivery

Nucleoprotein nanoparticles (NNPs) are assembled through specific interactions between zinc fingers and template DNAs on gold nanoparticles for targeted protein delivery. With controlled loading of a cytotoxic protein, the NNPs show a remarkable antitumor activity in xenograft mice. The NNPs find wide applications in biological and medical sciences. AbstractWith a growing number of intracellular drug targets and the high efficacy of protein therapeutics, the targeted delivery of active proteins with negligible toxicity is a challenging issue in the field of precision medicine. Herein, a programed assembly of nucleoprotein nanoparticles (NNPs) using DNA and zinc fingers (ZnFs) for targeted protein delivery is presented. Two types of ZnFs with different sequence specificities are genetically fused to a targeting moiety and a protein cargo, respectively. Double ‐stranded DNA with multiple ZnF‐binding sequences is grafted onto inorganic nanoparticles, followed by conjugation with the ZnF‐fused proteins, generating the assembly of NNPs with a uniform size distribution and high stability. The approach enables controlled loading of a protein cargo on the NNPs, offering a high cytosolic delivery efficiency and target specificity. The utility and potential of the assembly as a versatile protein delivery vehicle is demonstrated based on their remarkable antitumor activity and target specificity with negligible toxicity in a xenograft mice model.
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research