Fast and Efficient CRISPR/Cas9 Genome Editing In Vivo Enabled by Bioreducible Lipid and Messenger RNA Nanoparticles

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

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 33 vom: 17. Aug., Seite e1902575
1. Verfasser: Liu, Ji (VerfasserIn)
Weitere Verfasser: Chang, Jin, Jiang, Ying, Meng, Xiandi, Sun, Tianmeng, Mao, Lanqun, Xu, Qiaobing, Wang, Ming
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CRISPR/Cas9 genome editing lipid nanoparticles messenger RNA delivery Lipids RNA, Guide, CRISPR-Cas Systems RNA, Messenger Green Fluorescent Proteins 147336-22-9 mehr... CRISPR-Associated Protein 9 EC 3.1.- Proprotein Convertase 9 EC 3.4.21.-
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520 |a A main challenge to broaden the biomedical application of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat (CRISPR) associated protein 9) genome editing technique is the delivery of Cas9 nuclease and single-guide RNA (sgRNA) into the specific cell and organ. An effective and very fast CRISPR/Cas9 genome editing in vitro and in vivo enabled by bioreducible lipid/Cas9 messenger RNA (mRNA) nanoparticle is reported. BAMEA-O16B, a lipid nanoparticle integrated with disulfide bonds, can efficiently deliver Cas9 mRNA and sgRNA into cells while releasing RNA in response to the reductive intracellular environment for genome editing as fast as 24 h post mRNA delivery. It is demonstrated that the simultaneous delivery of Cas9 mRNA and sgRNA using BAMEA-O16B knocks out green fluorescent protein (GFP) expression of human embryonic kidney cells with efficiency up to 90%. Moreover, the intravenous injection of BAMEA-O16B/Cas9 mRNA/sgRNA nanoparticle effectively accumulates in hepatocytes, and knocks down proprotein convertase subtilisin/kexin type 9 level in mouse serum down to 20% of nontreatment. The leading lipid nanoparticle, BAMEA-O16B, represents one of the most efficient CRISPR/Cas9 delivery nanocarriers reported so far, and it can broaden the therapeutic promise of mRNA and CRISPR/Cas9 technique further 
650 4 |a Journal Article 
650 4 |a CRISPR/Cas9 
650 4 |a genome editing 
650 4 |a lipid nanoparticles 
650 4 |a messenger RNA delivery 
650 7 |a Lipids  |2 NLM 
650 7 |a RNA, Guide, CRISPR-Cas Systems  |2 NLM 
650 7 |a RNA, Messenger  |2 NLM 
650 7 |a Green Fluorescent Proteins  |2 NLM 
650 7 |a 147336-22-9  |2 NLM 
650 7 |a CRISPR-Associated Protein 9  |2 NLM 
650 7 |a EC 3.1.-  |2 NLM 
650 7 |a Proprotein Convertase 9  |2 NLM 
650 7 |a EC 3.4.21.-  |2 NLM 
700 1 |a Chang, Jin  |e verfasserin  |4 aut 
700 1 |a Jiang, Ying  |e verfasserin  |4 aut 
700 1 |a Meng, Xiandi  |e verfasserin  |4 aut 
700 1 |a Sun, Tianmeng  |e verfasserin  |4 aut 
700 1 |a Mao, Lanqun  |e verfasserin  |4 aut 
700 1 |a Xu, Qiaobing  |e verfasserin  |4 aut 
700 1 |a Wang, Ming  |e verfasserin  |4 aut 
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773 1 8 |g volume:31  |g year:2019  |g number:33  |g day:17  |g month:08  |g pages:e1902575 
856 4 0 |u http://dx.doi.org/10.1002/adma.201902575  |3 Volltext 
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