Premium
Programed Assembly of Nucleoprotein Nanoparticles Using DNA and Zinc Fingers for Targeted Protein Delivery
Author(s) -
Ryu Yiseul,
Kang Jung Ae,
Kim Dasom,
Kim SongRae,
Kim Seungmin,
Park Seong Ji,
Kwon SeungHae,
Kim KilNam,
Lee DongEun,
Lee Joongjae,
Kim HakSung
Publication year - 2018
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201802618
Subject(s) - nucleoprotein , dna , drug delivery , chemistry , nanoparticle , nanotechnology , cytosol , biophysics , computational biology , biology , biochemistry , materials science , enzyme
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.