한빛사 논문
성균관대학교
Trung Thanh Thacha, Do Hyun Baeb, Nam Hyeong Kima, Eun Sung Kanga, Bok Soo Leea, Kayoung Hanc, Minsuk Kwaka, Hojae Choia, JiYoung Nama, Taegeun Baed, Minah Suhc,e, Junho K. Hurf,g, and Yong Ho Kima,b,h,*
aSKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, South Suwon 16419, Korea
bDepartment of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, South Korea
cCenter for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Sungkyunkwan University, Suwon 16419, South Korea
dDepartment of Medicine, Graduate School, Kyung Hee University, Seoul 02447, South Korea
eDepartment of Nano Engineering, Sungkyunkwan University, Suwon 16419, South Korea
fDepartment of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, South Korea
gDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, South Korea
hBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, South Korea
*To whom correspondence should be addressed.
Abstract
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.
Keywords : delivery, dNP2 lipopeptides, gene editing, hyper‐accurate Cas9, nanosomes
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