Lipopeptide-Based Nanosome-Mediated Delivery of Hyperaccurate CRISPR/Cas9 Ribonucleoprotein for Gene Editing

Trung Thanh Thach, Do Hyun Bae, Nam Hyeong Kim, Eun Sung Kang, Bok Soo Lee, Kayoung Han, Minsuk Kwak, Hojae Choi, Ji Young Nam, Taegeun Bae, Minah Suh, Junho K. Hur, Yong Ho Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


A transient cytosolic delivery system for accurate Cas9 ribonucleoprotein is a key factor for target specificity of the CRIPSR/Cas9 toolkit. Owing to the large size of the Cas9 protein and a long negative strand RNA, the development of the delivery system is still a major challenge. Here, a size-controlled lipopeptide-based nanosome system is reported, derived from the blood-brain barrier-permeable dNP2 peptide which is capable of delivering a hyperaccurate Cas9 ribonucleoprotein complex (HypaRNP) into human cells for gene editing. Each nanosome is capable of encapsulating and delivering ≈2 HypaRNP molecules into the cytoplasm, followed by nuclear localization at 4 h post-treatment without significant cytotoxicity. The HypaRNP thus efficiently enacts endogenous eGFP silencing and editing in human embryonic kidney cells (up to 27.6%) and glioblastoma (up to 19.7% frequency of modification). The lipopeptide-based nanosome system shows superior delivery efficiency, high controllability, and simplicity, thus providing biocompatibility and versatile platform approach for CRISPR-mediated transient gene editing applications.

Original languageEnglish
Article number1903172
Issue number46
Publication statusPublished - 2019 Nov 1

Bibliographical note

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

All Science Journal Classification (ASJC) codes

  • Engineering (miscellaneous)
  • Chemistry(all)
  • Materials Science(all)
  • Biotechnology
  • Biomaterials


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