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Engineered AAV13 variants with enhanced transduction and co.fined spread

Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality co.trol Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China brain case biotechnology co. Ltd.ShenzhenGuangdong 518107China co.lege of Life Sciences Wuhan UniversityWuhanHubei 430072China Center for Excellence in brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the co.text of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first co.structed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells co.pared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

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Nanoparticle drug delivery system for the treatment of brain tumors:Breaching the blood–brain barrier

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2786-2789页

作者： Qiyu Tang Guo Zhao Hong Fang Yale Jiang Peiwen Ma Jiawei Zhoua Dongyan Liu Shujun Xing Gaoquan Li Nian Liu Huiyu Chen Shuhang Wang Ning Li Clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Chongqing Upgra biotechnology co. Ltd.Chongqing 401331China

To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in *** tumors enco.pass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other ***,BM are the most prevalent intracranial malignant tumor affecting approximately 20%-40%of cancer patients2.

关键词： Nanoparticle Drug delivery system Blood-brain barrier Tumor Glioma

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Protective function and mechanisms of soybean peptides on aluminum maltolate induced brain and liver toxicity on C57BL/6 mice

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Food Bioscience 2023年第2期52卷 1118-1127页

作者： Yaojun Ju Dingdong Bu Bingye Li Dai Cheng State Key Laboratory of Food Nutrition and Safety Tianjin University of Science&TechnologyTianjin300457China Tianxiang(Shandong)biotechnology co. Ltd.Room 1001Block H2Innovation Valley Industrial ParkHaichuan RoadLiuhang StreetJiningShandongChina

Excessive Al deposition has been implicated in the pathogenesis of multiple *** organic form aluminum maltolate(Al(mal)3),which is potentially ingested by daily diet and digestion,is more toxic than AlCl3 and *** polypeptide(SP)has beco.e a research hotspot because of its cheap raw material source and abundant biological ***,the protective effect of SP on chronic Al exposure-induced toxicity in mice is *** this study,the protective effects and mechanisms of SP on Al(mal)3-exposed mice were *** the in vitro tests,SP showed higher Al3+chelation and antioxidant activities than soybean *** it was validated in vivo that SP treatment can reduce the Al deposition and enhance antioxidant capacities in organs and tissues of C57BL/6 J mice exposed to Al(mal)*** treatment was found to significantly reduce Al induced toxicities in C57BL/6 J mice,such as body weight loss,co.nitive impairment,brain damage and liver *** was also observed that SP treatment significantly reduced apoptosis and AMPK de-activation induced by Al(mal)3 exposure as detected by Western *** together,SP showed protective effects on Al3+exposure-induced toxicity by reducing Al deposition,enhancing antioxidation,suppressing apoptosis and upregulating AMPK activity.

关键词： Aluminum toxicity Soybean peptides brain Liver Apoptosis AMPK

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Searching Clue of the Relationship between the Alteration of Bioactive Ingredients and the Herbal “Property” Transformation from Raw Rehmanniae Radix (<i>Sheng-Di-Huang</i>) to Steam-Heating-Processed Rehmanniae Radix (<i>Shu-Di-Huang</i>) by Chromatographic Fingerprint Analysis

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Chinese Medicine 2014年第2期5卷 47-60页

作者： Peishan Xie Longgang Guo Yu Zhao Daniel Bensky Erich Stoeger Guangdong UNION biotechnology Development co. Ltd. Guangzhou China Independent Scholar Seattle USA Nikyang Enterprise co. Ltd. Hong Kong China Plantasia GmbH Oberndorf Austria

“Di-Huang” (Rehmanniae Radix) is a peculiar Chinese herbal drug, the fresh root named “Xian-Di-Huang” (“Xian” means fresh;the co.merce is now rarely available), mild-baking-dried raw roots “Sheng-Di-Huang” (“Sheng” means raw) and steam-processed “Shu-Di-Huang” (“Shu” implies steam-processed). The both kinds of herbal drug exert different efficiencies with different property acco.ding to the traditional clinical theory. It would be of interest that searching the clue of why the therapeutic functions of the same drug differ between the pre- and post-processing. To disclose the co.prehensive alteration of the iridoids, saccharides and phenylethanoids occurred between the raw and steam-processed “Di-Huang”, the HPTLC and HPLC chromatographic fingerprint analysis has been carried out. The results showed that in the raw crude drug, the iridoids like catalpol is the major bioactive co.ponents, and the oligosaccharides co.position kept rather co.sistent;however, in the steam-processed Di-Huang, iridoids was almost disappeared and the oligosaccharides were hydrolyzed gradually through the repeated steam-heating process. The worst case showed only fructose was detected with other minor residual co.ponents in the root tuber. It is due to presumably the unco.trollable steaming process in folk workshops. Defining reasonably the boundary between the “Sheng-Di-Huang” (mild-baking-dried Rehmanniae radix) and “Shu-Di-Huang” (steaming processed Rehmanniae radix) set up by chromatographic fingerprint pattern and standardizing the process would be necessary for assuring the co.sistent quality of the co.mercial herbal drugs.

关键词： Rehmanniae Radix Di-Huang Processing Incurred Herbal-Property-Change Chromatographic Fingerprinting Meaningful Quality co.trol

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Tunneling nanotubes between rat primary astrocytes and C6 glioma cells alter proliferation potential of glioma cells

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Neuroscience Bulletin 2015年第3期31卷 371-378页

作者： Lei Zhang Yan Zhang State Key Laboratory of Biomembrane and Membrane biotechnology College of Life Sciences PKU-IDG/Mc Govern Institute for Brain Research Peking University

The tunneling nanotube （TNT） is a newly disco.ered, long and thin tubular structure between cells. In this study, we established a co.culture system for rat primary astrocytes and C6 glioma cells and found that TNTs formed between them. Most of the TNTs initiated from astrocytes towards C6 glioma cells. The formation of TNTs depended on p53. In addition, hydrogen peroxide increased the number of TNTs in the co.culture system. Established TNTs reduced the proliferation of C6 glioma cells. Our data suggest that TNTs between astrocytes and glioma cells facilitate substance transfer and therefore alter the properties, including the proliferation potential, of glioma cells.

关键词： tunneling nanotube astrocyte glioma proliferation p53

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Characterization and differential expression of three GnRH forms during reproductive development in cultured turbot Schophthalmus maximus

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Journal of Oceanology and Limnology 2018年第4期36卷 1360-1373页

作者： ZHAO Chunyan XU Shihong FENG Chengcheng LIU Yifan YANG Yang WANG Yanfeng XIAO Yongshuang SONG Zongcheng LIU Qinghua LI Jun Key Laboratory of Experimental Marine Biology Institute of Oceanology Chinese Academy of Sciences Qingdao 266071 China University of Chinese Academy of Sciences Beijing 100049 China Laboratory for Marine Biology and biotechnology Qingdao National Laboratory for Marine Science and Technology Qingdao 266237 China Weihai Shenghang Aquatic Product Science and Technology co. Ltd. Weihai 264200 China

Turbots( Schophthalmus maximus), one of the most important eco.omic marine flatfish species, fail to undergo final spawning and spermiation naturally under artificial farming co.ditions. In vertebrates, reproduction is regulated by the brain-pituitary-gonadal axis(BPG-axis), and gonadotropin releasing hormone(GnRH) is one of its key co.ponents. Therefore, to better understand the physiology of reproduction in the turbot, three of the genes enco.ing GnRH subtypes— sbGnRH, c GnRH-II and sGnRH —were cloned and sequenced by isolating the cDNA sequences. The localizations and patterns of expression of their mRNAs were also evaluated during seasonal gonadal development. All three mRNAs were expressed abundantly in the brain; sbGnRH and sGnRH mRNAs were also detected in the gonads and pituitary gland, and sbGnRH expression was much higher than that of sGnRH, indicating the critical role of sbGnRH in regulating the BPG-axis. Moreover, the brain expression patterns of sbGnRH and sGnRH mRNAs showed an increased trend during gonadal development, peaking in mature stages. This indicated the direct regulation of gonadal development by the GnRH system. In addition, c GnRH-II mRNA expression showed no significant variations, suggesting that c GnRH-II is not critically involved in the co.trol of reproduction. Further, the mRNA abundances of the three GnRH forms in the breeding season were significantly higher than those in immature and post-breeding stages in all analyzed brain areas. Therefore, we propose that sbGnRH is the most important hormone for the regulation of reproduction in turbot via the BPG-axis. These results will help in better understanding the reproductive endocrine mechanisms of turbots and lay the groundwork for additional studies aimed at co.paring the reproductive physiology of wild individuals with those raised under artificial co.ditions.

关键词： turbot GnRH brain gonad reproductive development

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea co.parative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been co.sidered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was co.firmed by T7E1 *** first co.bination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP co.ld be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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Dog-transmitted Rabies in Beijing, China

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Biomedical and Environmental Sciences 2017年第7期30卷 526-529页

作者： ZHANG Jing Yuan ZHANG Bi ZHANG Shou Feng ZHANG Fei LI Nan LIU Ye HU Rong Liang Laboratory of Epidemiology and Key Laboratory of Jilin Province for Zoonosis Prevention and co.trol Military Veterinary Research Institute Academy of Military Medical Sciences Changchun 130122 Jilin China Beijing Municipal Center for Animal Disease co.trol and Prevention Beijing 102600 China Jilin Jiahui biotechnology co. Ltd Changchun 130000 Jilin China

Rabies remains a co.tinuous threat to public health in Beijing. In this study, a total of 224 brain tissues were co.lected from suspected infected stray dogs within Beijing between January 2015 and December 2016. Among them, total of 67 samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies in Beijing is currently a relatively independent public health issue originating from local rabid dogs apart from the imported cases from elsewhere in the co.ntry. Because vaccination of unregistered dogs against rabies is still neglected in Beijing and other regions of China, national and local authorities should play central roles in all related aspects, such as development of policies, engagement of stakeholders for public and professional education, entire vaccination process, and animal management.

关键词： in from is of for China Dog-transmitted Rabies in Beijing

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The production of biobased diamines from renewable carbon sources: Current advances and perspectives

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Chinese Journal of Chemical Engineering 2021年第2期34卷 4-13页

作者： Xin Wang Siyuan Gao Jing Wang Sheng Xu Hui Li Kequan Chen Pingkai Ouyang State Key Laboratory of Materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjing 211816JiangsuChina Zhejiang Zhongshan Chemical Industry Group co.Ltd Huzhou 313100Chin

Bio-based diamines are co.sidered to be a promising alternative to traditional fossil-fuel-based diamines,the important platform chemical for the synthesis of polymer *** this review,the current status of the art of the synthesis of aliphatic and aromatic diamines from renewable biomass are *** the case of aliphatic diamines,we describe strategies for biologically producing diamines with different carbon numbers including 1,3-diaminopropane,1,4-butanediamine,1,5-pentanediamine,1,6-diaminohexane,1,8-diaminooctane,1,10-diaminodecane,and 1,*** addition,aromatic diamines produced from various kinds of renewable biomass,including lignin,cashew nut shell,and terpenoids,are reviewed ***,the application of typical diamines in synthesis of polyurethane and polyamide are also reviewed.

关键词： Aliphatic diamines Aromatic diamines Polyamide Polyurethane

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Surgical intervention co.bined with weight-bearing walking training improves neurological reco.eries in 320 patients with clinically co.plete spinal co.d injury:a prospective self-co.trolled study

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Neural Regeneration Research 2021年第5期16卷 820-829页

作者： Yansheng Liu Jia-Xin Xie Fang Niu Zhexi Xu Pengju Tan Caihong Shen Hongkun Gao Song Liu Zhengwen Ma Kwok-Fai So Wutian Wu Chen Chen Sujuan Gao Xiao-Ming Xu Hui Zhu Kunming International Spine and Spinal co.d Injury Treatment Center Kunming Tongren HospitalKunmingYunnan ProvinceChina Clinical Center for Spinal co.d Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina Department of Laboratory Animal Sciences Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Ophthalmology and State Key Laboratory of brain and co.nitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Guangdong-Hongkong-Macao Institute for Central Nervous System Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Re-Stem biotechnology Co.Ltd.SuzhouJiangsu ProvinceChina Spinal co.d and brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Biostatistics Indiana University School of MedicineIndianapolisINUSA

Although a large number of trials in the SCI field have been co.ducted,few proven gains have been realized for *** the present study,we determined the efficacy of a novel co.bination treatment involving surgical intervention and long-term weight-bearing walking training in spinal co.d injury(SCI)subjects clinically diagnosed as co.plete or American Spinal Injury Association Impairment Scale(AIS)Class A(AIS-A).A total of 320 clinically co.plete SCI subjects(271 male and 49 female),aged 16–60 years,received early(≤7 days,n=201)or delayed(8–30 days,n=119)surgical interventions to reduce intraspinal or intramedullary *** days post-surgery,all subjects received a weight-bearing walking training with the“Kunming Loco.otion Training Program(KLTP)”for a duration of 6 *** neurological deficit and reco.ery were assessed using the AIS scale and a 10-point Kunming Loco.otor Scale(KLS).We found that surgical intervention significantly improved AIS sco.es measured at 15 days post-surgery as co.pared to the pre-surgery baseline *** improvement of AIS sco.es was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise co.parisons of time points of 15 days,3 or 6 months indicating co.tinued improvement in walking sco.es during the 6-month *** co.clusion,co.bining surgical intervention within 1 month post-injury and weight-bearing loco.otor training promoted co.tinued and statistically significant neurological reco.eries in subjects with clinically co.plete SCI,which generally shows little clinical reco.ery within the first year after injury and most are permanently *** study was approved by the Science and Research co.mittee of Kunming General Hospital of PLA and Kunming Tongren Hospital,China and registered at ***(Identifier:NCT04034108)on July 26,2019.

关键词： American Spinal Injury Association Impairment Scale–A functional reco.ery human intramedullary deco.pression spinal co.d injury surgical intervention walking training

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