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cr uuu---uuuuu |
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231225s2020 xx |||||o 00| ||eng c |
| 024 |
7 |
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|a 10.1002/adma.202003537
|2 doi
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5 |
2 |
|a pubmed24n1054.xml
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|a (DE-627)NLM316228621
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|a (NLM)33053221
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Gong, Jing
|e verfasserin
|4 aut
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| 245 |
1 |
2 |
|a A Versatile Nonviral Delivery System for Multiplex Gene-Editing in the Liver
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| 264 |
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1 |
|c 2020
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| 336 |
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|a Text
|b txt
|2 rdacontent
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| 337 |
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 20.08.2021
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|a Date Revised 07.11.2023
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2020 Wiley-VCH GmbH.
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|a Recent advances in CRISPR present attractive genome-editing toolsets for therapeutic strategies at the genetic level. Here, a liposome-coated mesoporous silica nanoparticle (lipoMSN) is reported as an effective CRISPR delivery system for multiplex gene-editing in the liver. The MSN provides efficient loading of Cas9 plasmid as well as Cas9 protein/guide RNA ribonucleoprotein complex (RNP), while liposome-coating offers improved serum stability and enhanced cell uptake. Hypothesizing that loss-of-function mutation in the lipid-metabolism-related genes pcsk9, apoc3, and angptl3 would improve cardiovascular health by lowering blood cholesterol and triglycerides, the lipoMSN is used to deliver a combination of RNPs targeting these genes. When targeting a single gene, the lipoMSN achieved a 54% gene-editing efficiency, besting the state-of-art Lipofectamine CRISPRMax. For multiplexing, lipoMSN maintained significant gene-editing at each gene target despite reduced dosage of target-specific RNP. By delivering combinations of targeting RNPs in the same nanoparticle, synergistic effects on lipid metabolism are observed in vitro and vivo. These effects, such as a 50% decrease in serum cholesterol after 4 weeks of post-treatment with lipoMSN carrying both pcsk9 and angptl3-targeted RNPs, could not be reached with a single gene-editing approach. Taken together, this lipoMSN represents a versatile platform for the development of efficient, combinatorial gene-editing therapeutics
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|a Journal Article
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4 |
|a CRISPR/Cas9
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| 650 |
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4 |
|a cardiovascular disease
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| 650 |
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4 |
|a gene therapy
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| 650 |
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4 |
|a multiplex gene editing
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| 650 |
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4 |
|a nanoparticles
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| 650 |
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7 |
|a ANGPTL3 protein, human
|2 NLM
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| 650 |
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7 |
|a Angiopoietin-Like Protein 3
|2 NLM
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| 650 |
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7 |
|a Angiopoietin-like Proteins
|2 NLM
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| 650 |
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7 |
|a Drug Carriers
|2 NLM
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| 650 |
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7 |
|a Lipids
|2 NLM
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| 650 |
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7 |
|a Lipofectamine
|2 NLM
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| 650 |
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7 |
|a Proprotein Convertase 9
|2 NLM
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| 650 |
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7 |
|a EC 3.4.21.-
|2 NLM
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| 700 |
1 |
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|a Wang, Hong-Xia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Lao, Yeh-Hsing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Hu, Hanze
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Vatan, Naazanene
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Guo, Jonathan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Ho, Tzu-Chieh
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Huang, Dantong
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Li, Mingqiang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Shao, Dan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Leong, Kam W
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Advanced materials (Deerfield Beach, Fla.)
|d 1998
|g 32(2020), 46 vom: 14. Nov., Seite e2003537
|w (DE-627)NLM098206397
|x 1521-4095
|7 nnns
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| 773 |
1 |
8 |
|g volume:32
|g year:2020
|g number:46
|g day:14
|g month:11
|g pages:e2003537
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| 856 |
4 |
0 |
|u http://dx.doi.org/10.1002/adma.202003537
|3 Volltext
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|a AR
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|d 32
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|e 46
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|h e2003537
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