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Abstract
With 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.

Author information

Ryu Y1, Kang JA2, Kim D1, Kim SR3, Kim S4, Park SJ4, Kwon SH3, Kim KN3, Lee DE2, Lee JJ4,5, Kim HS1.
1
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea.
2
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongup, 56212, South Korea.
3
Division of Bio-Imaging, Korea Basic Science Institute (KBSI), Chuncheon, 24341, South Korea.
4
Department of Biochemistry, Kangwon National University, Chuncheon, 24341, South Korea.
5
Institute of Life Sciences (ILS), Kangwon National University, Chuncheon, 24341, South Korea