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 nanosystems with Ang II infusion can provide the possibility for in vivo gene editing in aorta.