CRISPR/Cas9 Delivery Mediated with Hydroxyl-Rich Nanosystems for Gene Editing in Aorta

Advanced Science
Xiaoping ZhangJie Du

Abstract

A CRISPR/Cas9 system has emerged as a powerful tool for gene editing to treat genetic mutation related diseases. Due to the complete endothelial barrier, effective delivery of the CRISPR/Cas9 system to vasculatures remains a challenge for in vivo gene editing of genetic vascular diseases especially in aorta. Herein, it is reported that CHO-PGEA (cholesterol (CHO)-terminated ethanolamine-aminated poly(glycidyl methacrylate)) with rich hydroxyl groups can deliver a plasmid based pCas9-sgFbn1 system for the knockout of exon 10 in Fbn1 gene. This is the first report of a polycation-mediated CRISPR/Cas9 system for gene editing in aorta of adult mice. CHO-PGEA/pCas9-sgFbn1 nanosystems can effectively contribute to the knockout of exon 10 in Fbn1 in vascular smooth muscle cells in vitro, which leads to the change of the phosphorylation of Smad2/3 and the increased expression of two downstream signals of Fbn1: Mmp-2 and Ctgf. For in vivo application, the aortic enrichment of CHO-PGEA/Cas9-sgFbn1 is achieved by administering a pressor dose of angiotensin II (Ang II). The effects of the pCas9-sgFbn1 system targeting Fbn1 demonstrate an increase in the expression of Mmp-2 and Ctgf in aorta. Thus, the combination of CHO-PGEA/pCas9-sgFbn1 n...Continue Reading

References

Jan 1, 1994·Circulation·J G PickeringJ M Isner
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·S ArmeanuS Nikol
Feb 25, 2003·Nature Genetics·Enid R NeptuneHarry C Dietz
Sep 27, 2007·Nature Reviews. Molecular Cell Biology·Peter ten Dijke, Helen M Arthur
Jul 3, 2010·EMBO Molecular Medicine·Ariela BenigniGiuseppe Remuzzi
May 9, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ahmed O ElzoghbyNazik A Elgindy
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Mar 31, 2015·Nature Genetics·Jing LiaoAlexander Meissner
Feb 26, 2016·Annual Review of Pathology·Cindy Park-Windhol, Patricia A D'Amore
Feb 27, 2016·Human Mutation·Aline VerstraetenBart Loeys
Jun 9, 2016·The Application of Clinical Genetics·Guglielmina PepeStefano Nistri
Jul 5, 2016·Biomaterials Science·Chen XuFu-Jian Xu
Oct 7, 2016·Chemical Society Reviews·Amrita SinghSouvik Maiti
Nov 17, 2016·Nature·Keiichiro SuzukiJuan Carlos Izpisua Belmonte
Mar 16, 2017·Nature Communications·Wenhan YuZhijian Wu
Apr 7, 2017·Nature Nanotechnology·Marilena Hadjidemetriou, Kostas Kostarelos
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Hong-Xia WangKam W Leong
Jun 20, 2018·Nature Nanotechnology·Manuel TonigoldVolker Mailänder

❮ Previous
Next ❯

Citations

Dec 25, 2019·Advanced Science·Wilke C de VriesBart Jan Ravoo
Nov 24, 2019·Advanced Drug Delivery Reviews·Cong-Fei XuJun Wang
Nov 22, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yu TaoMingqiang Li
Sep 27, 2020·Biomaterials·Nisakorn YodsanitShaoqin Gong
Dec 16, 2020·ACS Biomaterials Science & Engineering·Jie ShenXin Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
electrophoresis
Protein
atomic force microscopy
flow cytometry
Fluorescence
PCR
exome sequencing
dynamic light scattering
AFM

Software Mentioned

SPSS
living image
Image J

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.