PMID- 30398698 OWN - NLM STAT- MEDLINE DCOM- 20191007 LR - 20191007 IS - 1613-6829 (Electronic) IS - 1613-6810 (Linking) VI - 14 IP - 52 DP - 2018 Dec TI - Programed Assembly of Nucleoprotein Nanoparticles Using DNA and Zinc Fingers for Targeted Protein Delivery. PG - e1802618 LID - 10.1002/smll.201802618 [doi] AB - 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. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Ryu, Yiseul AU - Ryu Y AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea. FAU - Kang, Jung Ae AU - Kang JA AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongup, 56212, South Korea. FAU - Kim, Dasom AU - Kim D AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea. FAU - Kim, Song-Rae AU - Kim SR AD - Division of Bio-Imaging, Korea Basic Science Institute (KBSI), Chuncheon, 24341, South Korea. FAU - Kim, Seungmin AU - Kim S AD - Department of Biochemistry, Kangwon National University, Chuncheon, 24341, South Korea. FAU - Park, Seong Ji AU - Park SJ AD - Department of Biochemistry, Kangwon National University, Chuncheon, 24341, South Korea. FAU - Kwon, Seung-Hae AU - Kwon SH AD - Division of Bio-Imaging, Korea Basic Science Institute (KBSI), Chuncheon, 24341, South Korea. FAU - Kim, Kil-Nam AU - Kim KN AD - Division of Bio-Imaging, Korea Basic Science Institute (KBSI), Chuncheon, 24341, South Korea. FAU - Lee, Dong-Eun AU - Lee DE AD - Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute (KAERI), Jeongup, 56212, South Korea. FAU - Lee, Joong-Jae AU - Lee JJ AUID- ORCID: 0000-0002-3121-1420 AD - Department of Biochemistry, Kangwon National University, Chuncheon, 24341, South Korea. AD - Institute of Life Sciences (ILS), Kangwon National University, Chuncheon, 24341, South Korea. FAU - Kim, Hak-Sung AU - Kim HS AD - Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, South Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181106 PL - Germany TA - Small JT - Small (Weinheim an der Bergstrasse, Germany) JID - 101235338 RN - 0 (Nucleoproteins) RN - 0 (Proteins) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - DNA/*chemistry MH - Drug Delivery Systems MH - Humans MH - Mice MH - Nanoparticles/*chemistry MH - Nucleoproteins/*chemistry MH - Protein Binding MH - Proteins/*chemistry MH - Zinc Fingers OTO - NOTNLM OT - nanoparticles OT - nucleoproteins OT - protein delivery OT - self-assembly OT - targeted therapy EDAT- 2018/11/07 06:00 MHDA- 2019/10/08 06:00 CRDT- 2018/11/07 06:00 PHST- 2018/07/05 00:00 [received] PHST- 2018/09/29 00:00 [revised] PHST- 2018/11/07 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2018/11/07 06:00 [entrez] AID - 10.1002/smll.201802618 [doi] PST - ppublish SO - Small. 2018 Dec;14(52):e1802618. doi: 10.1002/smll.201802618. Epub 2018 Nov 6.