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Exosome-loaded biomaterials for tendon/ligament repair

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Biomaterials Translational 2024年第2期5卷 129-143页

作者： Haohan wang Yonglin Guo Yiwen Jiang Yingyu Ge Hanyi wang Dingyi Shi Guoyang Zhang Jinzhong Zhao Yuhao Kang liren wang Shanghai Jiao Tong University School of Medicine ShanghaiChina Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina School of Materials Science and Engineering East China University of Science and TechnologyShanghaiChina

Exosomes,a specialised type of extracellular vesicle,have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic *** the competence of key substances responsible for the delivery function was gradually elucidated,series of shortcomings exemplified by the limited stability still need to be ***,how to take maximum advantage of the biological characteristics of exosomes is of great ***,the comprehensive exploration and application of biomedical engineering has improved the availability of exosomes and revealed the future direction of exosomes combined with *** review delves into the present application of biomaterials such as nanomaterials,hydrogels,and electrospun scaffolds,serving as the carriers of exosomes in tendon/ligament *** pinpointing and exploring their strengths and limitations,it offers valuable insights,paving the way the future direction of biomaterials in the application of exosomes in tendon/ligament repair in this field.

关键词： biomaterials electrospinning exosomes hydrogel microspheres hydrogels nanoparticles

Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats

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Science China Life Sciences 2024年

作者： Dexin Zhang Rui Zheng Zhoutong Chen liren wang Xi Chen Lei Yang Yanan Huo Shuming Yin Dan Zhang Jiaxin Huang Xingang Cui Dali Li Hongquan Geng Department of Urology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of Urology Children's Hospital of Fudan University Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University

Primary hyperoxaluria type 1(PH1) is a severe hereditary disease, leading to the accumulation of oxalate in multiple organs, particularly the kidney. Hydroxyacid oxidase 1(HAO1), a pivotal gene involved in oxalate production, is an approved target for the treatment of PH1. In this study, we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1 c.290-2 A in vivo with lipid nanoparticles(LNP) delivered adenine base editing(ABE) mR NA. A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver, leading to the sustainable normalization of urinary oxalate(for at least 6 months) and complete rescue of the pathophysiology in PH1 rats. Additionally, a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over60% Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats. These findings suggest that the LNPmediated base-editing of Hao1 c.290-2 A is an efficient and safe approach to PH1 therapy, highlighting its potential utility in clinical settings.

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Improving thermal stability and light fastness of Acid Red 114 by incorporating its anions in a ZnAl-layered double hydroxides matrix

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Particuology 2012年第4期10卷 503-508页

作者： Haifeng Zhu liren wang Pinggui Tang Yongjun Feng Dianqing Li State Key Laboratory of Chemical Resource Engineering Belting University of Chemical TechnologyBeijing 100029China

Incorporation of anions of Acid Red 114 dye （1,3-naphthalenedisulfonic acid, 8-[2-[3,3＇-dimethyl-4＇-[2-[4- [l（4-methylphenyl）sulfonyl]oxy] phenyl]diazenyl] [1,1＇-biphenyl]-4-yl]diazenyl]-7-hydroxy-, disodium salt）（denoted as NPDA） into ZnAl-layered double hydroxides （LDHs） has been carried out by an anion- exchange method in an effort to improve their thermal stability and light fastness. After intercalation of NPDA anions, the interlayer distance of the LDHs increases from 0.87 to 2.18 nm, confirming their incorporation into the interlayer galleries of the LDHs host. Infrared spectroscopy and thermogravimetric analysis revealed the presence of host-guest interactions between LDHs layers and NPDA anions. The thermal stability of NPDA and ZnAI-NPDA-LDHs was compared by thermogravimetric-differential ther- mal analysis, UV-visible spectroscopy and infrared spectroscopy. It was found that the thermal stability of NPDA anions was markedly improved by incorporation into the ZnA1-LDHs matrix, while the light fastness was also enhanced.

关键词： Layered double hydroxidesAnion-exchangeIncorporationThermal stabilityLight fastness

CRISPR/Cas9 system： a powerful technology for in vivo and ex vivo gene therapy

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Science China(Life Sciences) 2017年第5期60卷 468-475页

作者： Xiaohui Zhang liren wang Mingyao Liu Dali Li Shanghai Key Laboratory of Regulatory Biology institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241 China

CRISPR/Cas9 is a versatile genome-editing tool which is widely used for modifying the genome of both prokaryotic and eukaryotic organisms for basic research and applications. An increasing number of reports have demonstrated that CRISPR/Cas9-mediated genome editing is a powerful technology for gene therapy. Here, we review the recent advances in CRISPR/Cas9-mediated gene therapy in animal models via different strategies and discuss the challenges as well as future prospects.

关键词： CRISPR/Cas9 gene therapy in vivo ex vivo

Corrigendum to“Long-term correction of hemophilia B through CRISPR/Cas9 induced homology-independent targeted integration”[Journal of Genetics and Genomics(2022)49,1114-1126]

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Journal of Genetics and Genomics 2024年第5期51卷 578-578页

作者： Xi Chen Xuran Niu Yang Liu Rui Zheng Lei Yang Jian Lu Shuming Yin Yu Wei Jiahao Pan Ahmed Sayed Xueyun Ma Meizhen Liu Fengxiang Jing Mingyao Liu Jiazhi Hu liren wang Dali Li Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China The MOE Key Laboratory of Cell Proliferation and Differentiation Genome Editing Research CenterSchool of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Xinhua Hospital Shanghai Jiao Tong University School of MedicineShanghai 200092China Biochemistry Laboratory Chemistry DepartmentFaculty of ScienceAssiut UniversityAssiut 71516Egypt Shanghai Turtle Technology Co. Shanghai 201900China

The authors regret that the grant number“21CJ1402200”in the Acknowledgments session should be replaced as“21JC1402200”.The corrected contents areprovided as follows.

关键词： CRISPR/Cas9 correction ledgment

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基于站城融合条件下的站台实际限界标准优化

铁道技术标准（中英文） 2024年第5期6卷 8-12页

作者：王立仁曹永霄陈晓明巨玉祥高原铁路运输智慧管控铁路行业重点实验室甘肃兰州730070 中铁第一勘察设计院集团有限公司线运院陕西西安710043 中国铁路兰州局集团公司武威南车务段甘肃武威733009 兰州交通大学交通运输学院甘肃兰州730070

现行的铁路站台建筑限界设计及其施工验收标准富裕量均较大,以适应各种复杂条件下高速铁路站台墙建设要求。但随着“站城融合”概念的提出,车站建成环境发生变化。相对外界而言,该类车站的建设封闭且稳定,停站车体受到外界“横风”影响... 详细信息

现行的铁路站台建筑限界设计及其施工验收标准富裕量均较大,以适应各种复杂条件下高速铁路站台墙建设要求。但随着“站城融合”概念的提出,车站建成环境发生变化。相对外界而言,该类车站的建设封闭且稳定,停站车体受到外界“横风”影响,产生的偏移量较小,因此,为提高旅客乘车安全性,站台建筑限界设计及施工验收标准也应相应进行调整。本文通过对影响铁路站台实际限界重要因素“横风”及施工质量验收标准进行分析,提出在站城融合条件下的旅客站台合理最小建筑限界值,为站城融合条件下车站站台的设计和施工提供参考,同时强化旅客乘车安全保障,提高客运服务质量,提升旅客乘车体验。

关键词：站城融合铁路站台实际建筑限界标准优化

Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair

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Bioactive Materials 2022年第10期7卷 149-161页

作者： liren wang Tonghe Zhu Yuhao Kang Jianguang Zhang Juan Du Haihan Gao Sihao Chen Jia Jiang Jinzhong Zhao Department of Sports Medicine Department of OrthopedicsShanghai Institute of Microsurgery on ExtremitiesShanghai Jiao Tong University Affiliated Sixth People’s HospitalNo.600 Yishan RoadShanghai200233China Regenerative Sports Medicine and Translational Youth Science and Technology Innovation Workroom Shanghai Jiao Tong University School of MedicineNo.227 South Chongqing RoadShanghai200025China Department of Medgen Group Research Laboratory 18 Qinglan 3 RdShenzhen518118China Biofunctional Materials Research Group College of Chemistry and Chemical EngineeringMultidisciplinary Center for Advanced MaterialsInstitute of Advanced StudiesShanghai University of Engineering ScienceNo.333 Longteng RdShanghai201620China Shanghai Jiao Tong University School of Medicine No.227 South Chongqing RoadShanghai200025China Regenerative Sports Medicine Lab of the Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People’HospitalNo.600 Yishan RoadShanghai200233China

Electrospun fibers,with proven ability to promote tissue regeneration,are widely being explored for rotator cuff ***,without post treatment,the microstructure of the electrospun scaffold is vastly different from that of natural extracellular matrix(ECM).Moreover,during mechanical loading,the nanofibers slip that hampers the proliferation and differentiation of migrating stem ***,electrospun nanofiber scaffolds,with crimped nanofibers and welded joints to biomimic the intricate natural microstructure of tendon-to-bone insertion,were prepared using poly(ester-urethane)urea and gelatin via electrospinning and double crosslinking by a multi-bonding network densification *** crimped nanofiber scaffold(CNS)features bionic tensile stress and induces chondrogenic differentiation,laying credible basis for in vivo *** repairing a rabbit massive rotator cuff tear using a CNS for 3 months,the continuous translational tendon-to-bone interface was fully regenerated,and fatty infiltration was simultaneously *** of micro-CT,μCT was employed to visualize the integrity and intricateness of the three-dimensional microstructure of the CNS-induced-healed tendon-to-bone interface at an ultra-high resolution of less than 1μ*** study sheds light on the correlation between nanofiber post treatment and massive rotator cuff repair and provides a general strategy for crimped nanofiber preparation and tendon-to-bone interface imaging characterization.

关键词： Massive rotator cuff tear Fatty infiltration Nanofiber scaffold Crimped structure Tendon-to-bone interface

Gene editing and its applications in biomedicine

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Science China(Life Sciences) 2022年第4期65卷 660-700页

作者： Guanglei Li Xiangyang Li Songkuan Zhuang liren wang Yifan Zhu Yangcan Chen Wen Sun Zeguang Wu Zhuo Zhou Jia Chen Xingxu Huang Jin wang Dali Li Wei Li Haoyi wang Wensheng Wei School of Life Science and Technology ShanghaiTech UniversityShanghai201210China Department of Clinical Laboratory Shenzhen Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People’s HospitalShenzhen518035China Shanghai Frontiers Science Research Base of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai200241China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100049China Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijing100101China Biomedical Pioneering Innovation Center Beijing Advanced Innovation Center for GenomicsPeking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking UniversityBeijing100871China Gene Editing Center School of Life Science and TechnologyShanghaiTech UniversityShanghai201210China Bejing Institute for Stem Cell and Regenerative Medicine Beijing100101China HIT Center for Life Sciences Harbin Institute of TechnologyHarbin150001China

The steady progress in genome editing, especially genome editing based on the use of clustered regularly interspaced short palindromic repeats(CRISPR) and programmable nucleases to make precise modifications to genetic material, has provided enormous opportunities to advance biomedical research and promote human health. The application of these technologies in basic biomedical research has yielded significant advances in identifying and studying key molecular targets relevant to human diseases and their treatment. The clinical translation of genome editing techniques offers unprecedented biomedical engineering capabilities in the diagnosis, prevention, and treatment of disease or disability. Here, we provide a general summary of emerging biomedical applications of genome editing, including open challenges. We also summarize the tools of genome editing and the insights derived from their applications, hoping to accelerate new discoveries and therapies in biomedicine.

关键词： gene editing CRISPR high-throughput functional genomics diagnostics animal model therapeutics

Long-term amelioration of an early-onset familial atrial fibrillation model with AAV-mediated in vivo gene therapy

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Fundamental Research 2022年第6期2卷 829-835页

作者： Handan Hu liren wang Huiying Li Hailing Li Xi Chen Wenhui Peng Jun wang Yongxiang Zhao Mingyao Liu Dali Li Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Southern Medical University Affiliated Fengxian Hospital Shanghai 201499China The Department of Cardiology Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China Department of Pediatrics McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTX 77030United States National Center for International Biotargeting Theranostics Guangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor TheranosticsGuangxi Medical UniversityGuangxi 530021China

Atrial fibrillation(AF)is a common cardiac disease with high prevalence in the general *** a mild manifestation at the onset stage,it causes serious consequences,including sudden death,when the disease progresses to the late *** available treatments of AF focus on symptom management or alleviation,due to a lack of fundamental knowledge and the fact that considerable variations of AF *** the popularisation of the next-generation sequencing technology,several causal genetic factors,including MYL4,have been discovered to contribute to AF,giving hope to developing its gene *** this study,we attempted to treat a previously established rat AF model,which carried Myl4E11K/E11K loss of function mutation,via overexpression of exogenous wild-type Myl4 by AAV9 *** results showed that delivery of Myl4 expressing AAV9 to postnatal rat models rescued the symptoms of AF,indicating the therapeutic potential that early gene therapy intervention can achieve long-term effects in treating cardiac arrhythmias caused by gene mutations.

关键词： Atrial fibrillation Gene therapy AAV 9Myl4 Genetic disorder