title: Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing.
abstract: CRISPR-Cas9 represents a promising platform for genome editing, yet means for its safe and efficient delivery remain to be fully realized. A novel vehicle that simultaneously delivers the Cas9 protein and single guide RNA (sgRNA) is based on DNA nanoclews, yarn-like DNA nanoparticles that are synthesized by rolling circle amplification. The biologically inspired vehicles were efficiently loaded with Cas9/sgRNA complexes and delivered the complexes to the nuclei of human cells, thus enabling targeted gene disruption while maintaining cell viability. Editing was most efficient when the DNA nanoclew sequence and the sgRNA guide sequence were partially complementary, offering a design rule for enhancing delivery. Overall, this strategy provides a versatile method that could be adapted for delivering other DNA-binding proteins or functional nucleic acids.
authors: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA).|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA).
authors: Wujin
authors: W
authors: Sun
authors: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA).|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA).
authors: Wenyan
authors: W
authors: Ji
authors: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695-7905 (USA).
authors: Jordan M
authors: JM
authors: Hall
authors: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA).|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA).
authors: Quanyin
authors: Q
authors: Hu
authors: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA).|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA).
authors: Chao
authors: C
authors: Wang
authors: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695-7905 (USA). cbeisel@ncsu.edu.
authors: Chase L
authors: CL
authors: Beisel
authors: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA). zgu@email.unc.edu.|Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA). zgu@email.unc.edu.|Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599 (USA). zgu@email.unc.edu.
authors: Zhen
authors: Z
authors: Gu
mesh_terms: D000818:Animals; D064130:CRISPR-Associated Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D064113:CRISPR-Cas Systems; D002460:Cell Line; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D000094704:RNA, Guide, CRISPR-Cas Systems / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000235:genetics
chemical_list: D064130:CRISPR-Associated Proteins; D000094704:RNA, Guide, CRISPR-Cas Systems; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA
keywords: CRISPR-Cas9; DNA; drug delivery; genome editing; nanoparticles