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| 1 | One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs显示文摘CRISPR/Cas9 系统是一个有效编辑基因的方法,但是编辑基因的动物的多数显示出 mosaicism,与编辑仅仅在房间的部分发生。这里,我们证明那单个基因或多重基因能被 Cas9 mRNA 和多重邻近的单个指南的 RNA 的 zygotic 注射完全在老鼠和猴子胚胎击倒(spaced 10-200 bp 分开) 指向仅仅一把单个钥匙每基因的 exon。个别地在 Y 染色体上跟随八基因的指向的删除的 F0 老鼠的 Phenotypic 分析在产生猛烈老鼠表明了这条途径的坚韧性。重要地,这条途径在高效率交付完全的基因大美人(Arntl 上的 100% 并且 91% 在 Prrt2 上) 在猴子胚胎。最后,我们能在一个单个步骤产生一只完全的 Prrt2 猛烈猴子,表明在很快建立编辑基因的猴子模型的这条途径的实用性。 | Erwei Zuo Yi-Jun Cai Kui Li Yu Wei Bang-An Wang Yidi Sun Zhen Liu Jiwei Liu Xinde Hu Wei Wei Xiaona Huo Linyu Shi Cheng Tang Dan Liang Yan Wang Yan-Hong Nie Chen-Chen Zhang Xuan Yao Xing Wang Changyang Zhou Wenqin Ying Qifang Wang Ren-Chao Chen Qi Shen Guo-Liang Xu Jinsong Li Qiang Sun Zhi-Qi Xiong Hui Yang | 2017 | Cell Research2017，27，7： | 21 |
| 2 | Highly efficient base editing in human tripronuclear zygotes显示文摘 | Changyang Zhou Meiling Zhang Yu Wei Yidi Sun Yun Sun Hong Pan Ning Yao Wanxia Zhong Yixue Li Weiping Li3 Hui Yang Zi-jiang Chen | 2017 | Protein & Cell2017，8，10： | 6 |
| 3 | Indiscriminate ssDNA cleavage activity of CRISPR-Cas12a induces no detectable off-target effects in mouse embryos显示文摘Dear Editor,Newly discovered characteristics like'collateral effect'or trans-cleavage in CRISPR-Cas13 and CRISPR-Cas12 systems have enabled their usage in nucleic acid detection(Gootenberg et al.2017,2018;Chen et al.2018).The collateral RNA cleavage of Cas13a has been reported to be harmful for cell development(Wang et al.2019;Buchman et al.2020).As a representative gene editor of CRISPR-Cas12 system,CRISPR-Cas12a(Cpf1)holds great potential for therapeutic applications in the future(Zetsche et al.2015;Koo et al.2018;Campa et al.2019). | Yu Wei Yingsi Zhou Yajing Liu Wenqin Ying Ruiming Lv Qimeng Zhao Haibo Zhou Erwei Zuo Yidi Sun Hui Yang Changyang Zhou | 2021 | Protein & Cell2021，12，9： | 2 |
| 4 | CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration显示文摘RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro.In this perspective,we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown in vivo could prevent the development of laser-induced CNV in mouse model of Age-related macular degeneration. | Changyang Zhou Xinde Hu Cheng Tang Wenjia Liu Shaoran Wang Yingsi Zhou Qimeng Zhao Qiyu Bo Linyu Shi Xiaodong Sun Haibo Zhou Hui Yang | 2020 | National Science Review2020，7，5： | 2 |
| 5 | Structural Topology and Dynamic Response Analysis of an Electric Torque Vectoring Drive-Axle for Electric Vehicles显示文摘In-wheel motor-drive electric vehicles have the advantage of independently controllable wheel torque and the disadvantages of unsprung mass rise and power restriction.To address the disadvantages,a centralized layout electric torque vectoring drive-axle system(E-TVDS)with dual motors is proposed,which can realize arbitrary distribution of driving torque between the left and right wheels.First,the speed and torque distribution principle of E-TVDS based on velocity diagram are analyzed,and a virtual prototype of the whole vehicle with basic gear ratio relation model of the E-TVDS is built for simulation to verify the theoretical results and the basic effect of E-TVDS on the steering performance of the vehicle.Second,the charac-teristics of 36 types of the novel E-TVDS topology structure are compared and analyzed,and the optimal structure scheme is selected.Third,the accurate multiple degrees of freedom dynamic model for the optimal structure is established by using the bond graph method,and its dynamic response characteristics are analyzed.The results show that the vehicle equipped with the proposed E-TVDS can distribute the driving torque with the almost identical amount but opposite sign between the left and right wheels in any direction,and varying amount according to different chassis dynamics control requirements,and the torque response performance is great with little delay and overshoot.The function and dynamic response of the proposed E-TVDS show that it has potential application value for various performance improvements of electric vehicles. | Junnian Wang Shoulin Gao Yue Qiang Meng Xu Changyang Guan Zidong Zhou | 2022 | Automotive Innovation2022，5，2： | 1 |
| 6 | Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice显示文摘We here report a genome-editing strategy to correct spinal muscular atrophy(SMA).Rather than directly targeting the pathogenic exonic mutations,our strategy employed Cas9 and guide-sg RNA for the targeted disruption of intronic splicing-regulatory elements.We disrupted intronic splicing silencers(ISSs,including ISS-N1 and ISS+100)of survival motor neuron(SMN)2,a key modifier gene of SMA,to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs.Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration.Furthermore,co-injection of Cas9 mRNA from Streptococcus pyogenes(SpCas9)or Cas9 from Staphylococcus aureus(SaCas9)alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56%and 100%of severe SMA transgenic mice(Smn-/-,SMN2tg/-).The median survival of the resulting mice was extended to>400 days.Collectively,our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. | Jin-Jing Li Xiang Lin Cheng Tang Ying-Qian Lu Xinde Hu Erwei Zuo He Li Wenqin Ying Yidi Sun Lu-Lu Lai Hai-Zhu Chen Xin-Xin Guo Qi-Jie Zhang Shuang Wu Changyang Zhou Xiaowen Shen Qifang Wang Min-Ting Lin Li-Xiang Ma Ning Wang Adrian R.Krainer Linyu Shi Hui Yang Wan-Jin Chen | 2020 | National Science Review2020，7，1： | 1 |
| 7 | Allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci using Staphylococcus aureus Cas9(SaCas9)显示文摘Allele-specific DNA methylation is the most important imprinting marker localized to differentially methylated regions(DMRs),and aberrant genomic imprinted DNA methylation is associated with some human diseases,including Prader-Willi syndrome and cancer.Thus,the development of an effective strategy for the precise editing of allele-specific methylated genes is essential for the functional clarification of imprinting elements and the correction of imprinting disorders in human diseases.To discover a feasible allele-specific genome editing tool based on the CRISPR/Cas system,which is an efficient genetargeting technique in various organisms,we examined the targeting efficiency of Staphylococcus aureus Cas9(SaCas9)and Streptococcus pyogenes Cas9(SpCas9)in response to DNA methylation interference.We found that the targeting efficiency of SaCas9,but not SpCas9,was enhanced by targeted DNA demethylation using the d Cas9-Tet1 catalytic domain(CD)but suppressed by targeted DNA methylation using Dnmt3l-Dnmt3a-d Cas9.An in vitro cleavage assay further demonstrated that SaCas9 nuclease activity was inhibited by 5-methylcytosine(5mC)in a synthesized Cp G-containing context.Further analysis with Ch IP-Q-PCR demonstrated that the non-methylated sequence targeting of Sa Cas9 depends on the binding preference of SaCas9 to non-methylated sequences.Taking advantage of this feature of SaCas9,we have successfully obtained non-methylated allele-biased targeted embryos/mice for two imprinting genes,H19 and Snrpn,with relatively high efficiencies of 28.6%and 47.4%,respectively.These results indicate that the targeting efficiency of SaCas9 was strongly reduced by DNA methylation.By using SaCas9,we successfully achieved allele-specific genome editing of imprinting genes by preferentially targeting non-methylated loci. | Yajing Liu Jianan Li Changyang Zhou Bin Meng Yu Wei Guang Yang Zongyang Lu Qingmei Shen Yu Zhang Hui Yang Yunbo Qiao | 2019 | Science Bulletin2019，64，21： | 1 |
| 8 | Chemical constituents and anticoagulant activity from Delphinium brunonianum Royle显示文摘Delphinium brunonianum Royle belongs to Ranunculaceae family and has the effects of dispelling wind to relieve itching and cooling blood to detoxify.It was found that the extracts of D.brunonianum had good anticoagulant activity which was extracted with 70%ethanol in our previous researches.Then,16 compounds were isolated and identified from the extract of D.brunonianum,among which compounds 5,7-10,12,14,15-16 were isolated from this genus for the first time,and compounds 2-4 were isolated from this plant for the first time.And the coagulation activity assay showed that compounds 10,14 and 15 had good anticoagulant activity by activated partial thromboplastin time(APTT),thrombin time(TT)and prothrombin time(PT)in vitro. | Changyang Ma Sitan Chen Syed Arif Hussain Rizvi Huihui Zhou Wenyi Kang Xuefeng Xi Zhenhua Liu | 2024 | Journal of Future Foods2024，4，3： | 0 |
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