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Adeno-associated virus as a delivery vector for gene therapy of human diseases

Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei Zhan Thomas L.Gallagher guangping gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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Is smaller better?Vaccine targeting recombinant receptorbinding domain might hold the key for mass production of effective prophylactics to fight the COVID-19 pandemic

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Signal Transduction and Targeted Therapy 2020年第1期5卷 637-639页

作者： Manish Muhuri guangping gao Horae Gene Therapy Center University of Massachusetts Medical SchoolWorcesterMAUSA Department of Microbiology and Physiological Systems University of Massachusetts Medical SchoolWorcesterMAUSA Li Weibo Institute for Rare Diseases Research University of Massachusetts Medical SchoolWorcesterMAUSA

A recent report by Yang et *** in Nature reported a recombinant vaccine utilizing recombinant receptor-binding domain(RBD)of SARS-CoV-2 Spike Protein.1 This vaccine candidate successfully induced potent functional antibody responses in the immunized mice,rabbits,and non-human *** study highlights the critical role of the immunogenicity of the RBD domain upon SARS-CoV-2 infection and the alternate vaccine designs that could serve as effective prophylactics against the pandemic.

关键词： vaccine al Vaccine

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Viral vector platforms within the gene therapy landscape

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Signal Transduction and Targeted Therapy 2021年第3期6卷 664-687页

作者： Jote T.Bulcha Yi Wang Hong Ma Phillip W.L.Tai guangping gao Horae Gene Therapy Center University of Massachusetts Medical SchoolWorcesterMAUSA Department of Microbiology and Physiological Systems University of Massachusetts Medical SchoolWorcesterMAUSA Department of Pathophysiology West China College of Basic medical sciences&Forensic MedicineSichuan UniversityChengduChina VIDE Program University of Massachusetts Medical SchoolWorcesterMAUSA Li Weibo Institute for Rare Diseases Research University of Massachusetts Medical SchoolWorcesterMAUSA

Throughout its 40-year history,the field of gene therapy has been marked by many *** has seen great strides in combating human disease,has given hope to patients and families with limited treatment options,but has also been subject to many *** of patients with this class of investigational drugs has resulted in severe adverse effects and,even in rare cases,*** the heart of this dichotomous field are the viral-based vectors,the delivery vehicles that have allowed researchers and clinicians to develop powerful drug platforms,and have radically changed the face of *** the past 5 years,the gene therapy field has seen a wave of drugs based on viral vectors that have gained regulatory approval that come in a variety of designs and purposes,these modalities range from vector-based cancer therapies,to treating monogenic diseases with life-altering *** present,the three key vector strategies are based on adenoviruses,adeno-associated viruses,and *** have led the way in preclinical and clinical successes in the past two ***,despite these successes,many challenges still limit these approaches from attaining their full *** review the viral vector-based gene therapy landscape,we focus on these three highly regarded vector platforms and describe mechanisms of action and their roles in treating human disease.

关键词： drugs landscape approval

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Screening of Chinese Herbal Medicines against Avian Infectious Laryngotracheitis Virus and Escherichia coli

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Agricultural Biotechnology 2013年第5期2卷 25-27,31页

作者： Yanying ZHANG Qiumei SHI Guisheng gao guangping gao Ping SHEN Key Laboratory of Preventive Veterinary Medicine of Hebei Province College of Animal Science and TechnologyHebei Normal University of Science and Technology

[ Objective] This study aimed to screen Chinese herbal medicines against avian infectious laryngotracheitis virus and Escherichia coli. [ Method ] Conventional Chinese medicine plate dilution method, plate punching method and test tube method were applied to screen Chinese herbal medicines against avian infectious laryngotracheitis virus based on chicken embryo inoculation experiment. [ Result ] Forsythia suspensa, Radix lsatidis, Isatis iadigotica, Lonicera japonica, Codonopsis pilosula, Astragalus membranaceus, Rhizoma Atractylodis Macrocephalae, C, tyeyrrhiza uralensis and Pericarpium granati had relatively strong anti-ILTV effect; among the Chinese herbal medicines against avian E. coli, Sanguisorba offwinalis, Fructus Mume, Rheum palmatum, Anemarrhena asphodeloides, Radix Scutellariae and Fagopyrum cymosum had relatively strong effect against avian E. coli Os, while other Chinese herbal medicines had relatively weak or no inhibitory effect on avian E. coli 0s and 05. [ Conclusion] This study laid the foundation for further development of Chinese herbal medicine compound preparations to treat avian infectious laryngotracheitis, avian colibacillosis and other viral diseases and bacterial diseases.

关键词： Chinese herbal medicine Screening Avian infectious laryngotracheitis virus Escherichia coli

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Regulation effects of water and nitrogen on yield,water,and nitrogen use efficiency of wolfberry

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Journal of Arid Land 2024年第1期16卷 29-45页

作者： gao Yalin QI guangping MA Yanlin YIN Minhua WANG Jinghai WANG Chen TIAN Rongrong XIAO Feng LU Qiang WANG Jianjun College of Water Conservancy and Hydropower Engineering Gansu Agricultural UniversityLanzhou 730070China Jingtaichuan Electric Power Irrigation Water Resource Utilization Center in Gansu Province Baiyin 730900China

Wolfberry(Lycium barbarum L.)is important for health care and ecological ***,it faces problems of low productivity and resource utilization during *** reasonable models for water and nitrogen management is important for solving these *** on field trials in 2021 and 2022,this study analyzed the effects of controlling soil water and nitrogen application levels on wolfberry height,stem diameter,crown width,yield,and water(WUE)and nitrogen use efficiency(NUE).The upper and lower limits of soil water were controlled by the percentage of soil water content to field water capacity(θ_(f)),and four water levels,i.e.,adequate irrigation(W0,75%-85%θ_(f)),mild water deficit(W1,65%-75%θ_(f)),moderate water deficit(W2,55%-65%θ_(f)),and severe water deficit(W3,45%-55%θ_(f))were used,and three nitrogen application levels,i.e.,no nitrogen(N0,0 kg/hm^(2)),low nitrogen(N1,150 kg/hm^(2)),medium nitrogen(N2,300 kg/hm^(2)),and high nitrogen(N3,450 kg/hm^(2))were *** results showed that irrigation and nitrogen application significantly affected plant height,stem diameter,and crown width of wolfberry at different growth stages(P<0.01),and their maximum values were observed in W1N2,W0N2,and W1N3 *** weight per plant and yield of wolfberry first increased and then decreased with increasing nitrogen application under the same water *** weight per hundred grains and dry weight percentage increased with increasing nitrogen application under W0 ***,under other water treatments,the values first increased and then decreased with increasing nitrogen *** and its component of wolfberry first increased and then decreased as water deficit increased under the same nitrogen *** water use efficiency(IWUE,8.46 kg/(hm^(2)·mm)),WUE(6.83 kg/(hm^(2)·mm)),partial factor productivity of nitrogen(PFPN,2.56 kg/kg),and NUE(14.29 kg/kg)reached their highest values in W2N2,W1N2,W1N2,and W1N1 treatments.R

关键词： water deficit growth characteristics yield water and nitrogen use efficiency principal component analysis

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Effects of Two Drugs on Small Intestinal Epithelial Lymphocytes of Experimental Piglets with Spleen Deficiency

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Agricultural Biotechnology 2013年第4期2卷 34-37页

作者： Ping SHEN Yanying ZHANG Guisheng gao Qiumei SHI guangping gao Xinhua SHAO Key Laboratory of Preventive Veterinary Medicine of Hebei Province Hebei Normal University of Science and Technology Hebei Xinhua Animal Drug Co. Ltd.

[ Objective] This study aimed to investigate the effects of Guchang Cuzhang powder and Smecta on small intestinal epithelial lymphocytes of piglets with spleen deficiency and diarrhea induced by Reserpine. [ Method] Eighteen piglets with reserpine-induced spleen deficiency and diarrhea were selected and randomly divided into three groups, six per group, including Guchang Cuzhang powder group, Smeeta group and spleen deficiency control group. Piglets in two drug adnfinistration groups were treated for 7 d using Guchang Cuzhang powder and Smecta, respectively. On the 2nd d and 8th d after drug withdrawal, three piglets in each group were euthanized by jugular vein bleeding to death. Intestine segments in different groups were collected for paraffin embedding, section preparation and HE staining, to conduct histological observation and count the number of small intestinal epithelial lymphocytes. [ Result ] Compared with the spleen deficiency control group, the number of lymphocytes in small intestinal epithelium of piglets in two drug administration groups increased significantly; in addition, the number of lymphocytes in small intestinal epithelium of piglets in Guchang Cuzhang powder group was significantly higher than that in Smecta group. [ Conclusion ] This study provided theoretical basis for the clinical applieation of Guchang Cuzhang powder and Smecta.

关键词： Piglets Guchang Cuzhang powder Smecta Spleen deficiency Small intestine Lymphocyte

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Effect of Echinacea Polysaccharide on Secretion of IL-1αmRNA by IEC-6 Injured by LPS

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Agricultural Biotechnology 2016年第6期5卷 35-36,43页

作者： Yanying ZHANG Qiumei SHI Qinghui JIA Guisheng gao guangping gao Xinhua SHAO Hebei Normal University of Science&Technology Hebei Province Key Laboratory of Preventive Veterinary MedicineChangli 066600China Xinhua Keji Veterinary Medicine Co. Ltd.of Hebei ProvinceLuancheng 051430China

[ Objective ] This study was conducted to investigate Echinacea polysaccharide （EPS） on expression of tumor necrosis factor （TNF） under injury of intestinal epithelial cells （IEC-6） by lipopolysaccharide （LPS）, so as to discuss the action mechanism of EPS to injured cells. [Method] Total DNA was extracted with TRIzon reagent, TNF-α mRNA was amplified, and the amplification products were subjected to agarose gel electrophoresis and imaging. [Result] 50 μg/ml EPS could partially inhibited the production of IL-α mRNA by IEC-6 under the stimulation of LPS, while the inhibition of 2（10 and 500 μg/ml EPS on the level of IL-1α mRNA gradually increased with the concentration increasing; and IEC-6 cells pretreated with 50,100,200 and 500 μg/ml EPS for 24 h and then stimulated by 10 μml IPS for 1 and 4 h were analyzed by RT-PCR method, and it was found that the expression of IL-α mRNA induced by LPS could be effectively inhibited by EPS, and the inhibition rate at 4 h was higher than that at 1 h. [ Conclusion] EPS could play its role of protecting intestinal mucosa by inhibiting the secretion of IL-1α mRNA by cells under the stimulation of LPS, and such inhibition effects of EPS had concentration dependency and time dependency.

关键词： Echinacea pelysaccharide Lipopelysaccharide Intestinal epithelial cell Inhibition Protection IL-1αmRNA

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Histopathological Observation of Classical Swine Fever in Newborn Piglets

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Agricultural Biotechnology 2013年第5期2卷 45-47,51页

作者： Ping SHEN Guisheng gao Yanying ZHANG Qiumei SHI guangping gao Zhipeng LI Key Laboratory of Preventive Veterinary Medicine of Hebei Province Hebei Normal University of Science and Technology

[ Objective] This study aimed to investigate pathological changes in various organs of piglets infected with classical swine fever and provide reliable basis for accurate diagnosis of classical swine fever. [ Method] By using paraffin embedding, section slicing and HE staining, histopathological changes in the heart, liver, spleen, lung, kidney and small intestine tissues of five diseased piglets were observed. C Result] Classical swine fever virus could lead to multiple visceral and mueosal hemorrhages, inflammatory cell infiltration, necrosis and other pathological changes. [ Conclusion ] Classical swine fever virus can further cause progressive degeneration and necrosis of different cells, resulting in immune injury.

关键词： Piglet Classical swine fever Histopathology Parenchymal organ

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In Vitro Antibacterial Effect of Traditional Chinese Medicine on Main Pathogenic Bacteria of Recessive Mastitis in Dairy Cows

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Animal Husbandry and Feed Science 2017年第1期9卷 34-36页

作者： gao Guisheng Hu Tiefeng An Jiwei gao guangping Shi Qiumei Shao Xinhua Zhang Yanying Hebei Provincial Key Laboratory of Veterinary Preventive Medicine Hebei Normal University of Science and TechnologyChangli 066600China Animaland Veterinary Bureau of Laoting County Tangshan 063600China Hebei Xinhua Veterinary Drug Co. Ltd.Luancheng 051430China

The inhibition zone diameter, minimal inhibitory concentration （MIC） and minimum bactericidal concentration （MBC） of 20 kinds of traditional Chi- nese medicine on Staphylococcus aureus and Streptococcus agalactiae isolated from recessive mastitis were studied using plate test and tube test. The results showed that S. aureus and S. agalactiae were sensitive to all these 20 kinds of traditional Chinese medicine, and were more sensitive to seven kinds of traditional Chinese medicine, including Taraxtwum mongolicum, Coptis chinensis, Forsythia suspense, Andrographis paniculata, Carthamus tinctorius, Scutellaria baicalensis and Den- dranthema indicum.

关键词： Traditional Chinese medicine Streptococcus agalactiae Inhibition zone diameter MIC MBC

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Effects of Echinacea Polysaccharide on Expression of NF-κB Protein Secreted by LPS-injured IEC-6 Cells

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Animal Husbandry and Feed Science 2017年第1期9卷 32-33,40页

作者： Shi Qiumei Zhang Yanying Jia Qinghui gao Guisheng gao guangping Wang Jinfeng Zhang Donglin Hebei Provincial Key Laboratory of Veterinary Preventive Medicine Hebei Normal University of Science and TechnologyChangli 066600China Yongqing Animal Husbandry and Veterinary Bureau Yongqing 065600China

[ Objective ] The paper was to explore effects of Echinacea polysaccharide （EPS） on expression of NF-KB protein secreted by LPS-injured IEC-6 cells, and to provide a theoretical basis for clinical application of Echinacea purpurea against bacterial diseases and enhancement of immunity. [ Method] Nucleoprotein extracted from IEC-6 cells in normal control group, LPS group, different concentrations of EPS （50, 100,200,500 μg/mL）＋ LPS groups were detected by SDS- PAGE electrophoresis, and the content of NF-κB protein was analyzed using western blotting method. [ Result ] The content of NF-KB protein in normal control group was the lowest, while that in LPS group was the highest. The content of NF-κB protein in EPS group gradually decreased with the increasing concentration of EPS. [ Result] The expression of NF-κB protein increased when IEC-6 cells were stimulated by LPS, and EPS could effectively inhibit increased expression of NF- κB protein. With the increasing concentration of EPS, the inhibition effect against increased expression of NF-κB protein gradually strengthened.

关键词： EPS NF-κB protein LPS IEC-6 ceils

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