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CRISPR,CAR-T,and NK:Current applications and future perspectives

genes & Diseases 2024年第4期11卷 246-257页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Amir Ali Hamidieh Saman Hosseinkhani Department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom branch***Iran national Institute of genetic Engineering and Biotechnology(NIGEB) Tehran 14965/161Iran Department of stem cells technology and Tissue Regeneration Faculty of Interdisciplinary Science and TechnologiesTarbiat Modares UniversityTehran 15614Iran Pediatric cell therapy and gene therapy research center GeneCell&Tissue Research InstituteTehran University of Medical SciencesTehran ***Iran Department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 15614Iran

Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer *** this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy *** the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been *** killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity *** on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the *** methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer *** improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor *** achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed inthis review.

关键词： Cancer CAR T-cell CRISPR gene editing Immunotherapy NK cell

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PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

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Zoological research 2024年第5期45卷 1037-1047页

作者： Chun-Xue Niu Jia-Wei Li Xiao-Li Li Lin-Lin Zhang Yan Lang Zhen-Bo Song Chun-Lei Yu Xiao-Guang Yang Hai-Feng Zhao Jia-Ling Sun Li-Hua Zheng Xue Wang Ying Sun Xiao-Hong Han Guan-Nan Wang Yong-Li Bao national Engineering Laboratory for Druggable gene and Protein Screening Northeast Normal UniversityChangchunJilin 130117China China international Joint research center for Human Stem cell Bank Northeast Normal UniversityChangchunJilin 130117China Jilin Institute for Drug Control ChangchunJilin 130022China

Serine protease 50(PRSS50/TSP50)is highly expressed in *** study investigated its role in testicular development and ***,PRSS50 knockdown was observed to impair DNA synthesis in *** further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male ***,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic *** analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−*** together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

关键词： PRSS50(TSP50) Meiotic progression Sperm quality MKP3 ERK

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Clinical applications of the CRISPR/Cas9 genome-editing system: Delivery options and challenges in precision medicine

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genes & Diseases 2024年第1期11卷 268-282页

作者： Mohadeseh Khoshandam Hossein Soltaninejad Marziyeh Mousazadeh Amir Ali Hamidieh Saman Hosseinkhani Department of Reproductive Biology Academic Center for EducationCultureand Research(ACECR)Qom BranchQom ***Iran national Institute of genetic Engineering and Biotechnology(NIGEB) Tehran 14155-6463Iran Faculty of Interdisciplinary Science and Technology Tarbiat Modares UniversityTehran 14117-13116Iran Pediatric cell and gene therapy research center GeneCell&Tissue Research InstituteTehran UniversityofMedical SciencesTehran14155-6559Iran Department of Nanobiotechnology Faculty of Biological SciencesTarbiat Modares UniversityTehran 14117-13116Iran Department of Biochemistry Faculty of Biological SciencesTarbiat Modares UniversityTehran 14117-13116Iran

CRISPR/Cas9 is an effective gene editing tool with broad applications for the pre-vention or treatment of numerous *** depends on CRiSPR(clustered regularly inter-spaced short palindromic repeats)as a bacterial immune system and plays as a gene editing *** to the higher specificity and efficiency of CRISPR/Cas9 compared to other editing ap-proaches,it has been broadly investigated to treat numerous hereditary and acquired ill-nesses,including cancers,hemolytic diseases,immunodeficiency disorders,cardiovascular diseases,visual maladies,neurodegenerative conditions,and a few X-linked ***/Cas9 system has been used to treat cancers through a variety of approaches,with sta-ble gene editing ***,the applications and clinical trials of CRisPR/Cas9 in various illnesses are *** to its high precision and efficiency,CRISPR/Cas9 strategies may treat gene-related illnesses by deleting,inserting,modifying,or blocking the expression of specific *** most challenging barrier to the in vivo use of CRISPR/Cas9 like off-target effects will be *** use of transfection vehicles for CRISPR/Cas9,including viral vectors(such as an Adeno-associated virus(AAV),and the development of non-viral vectors is also considered.

关键词： Clinical trials CRISPR/Cas9 gene therapy Non-viral vectors Viral vectors

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Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China national Clinical research center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China national Engineering research Centre of cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

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Recent advancement of sonogenetics:A promising noninvasive cellular manipulation by ultrasound

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genes & Diseases 2024年第5期11卷 163-182页

作者： Jin Tang Mingxuan Feng Dong Wang Liang Zhang Ke Yang Pediatric research Institute Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Engineering Research Center of Stem Cell TherapyChongqing 400014China Department of Ultrasound The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Tongji Medical College Huazhong University of Science and TechnologyWuhanHubei 430074China

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation ***,a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells,is gaining prominence along with optogenetics,electrogenetics,and *** stimulation with ultrasound,these proteins trigger a cascade of cellular activities and *** traditional ultrasound modalities,sonogenetics offers enhanced spatial selectivity,improving precision and safety in disease *** technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications,including neuromodulation,oncologic treatments,stem cell therapy,and *** current literature predominantly emphasizes ultrasonic neuromodulation,this review offers a comprehensive exploration of *** discuss ultrasound properties,the specific ultrasound-sensitive proteins employed in sonogenetics,and the technique’s potential in managing conditions such as neurological disorders,cancer,and ophthalmic diseases,and in stem cell *** objective is to stimulate fresh perspectives for further research in this promising field.

关键词： Mechanosensitive channel Neuromodulation Sonogenetics Ultrasound Ultrasound-sensitive protein

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Heptamethine cyanines in bioorthogonal chemistry

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Chinese Chemical Letters 2024年第2期35卷 131-137页

作者： Yuanyuan Liao Yuting Liang Yurou Huang Xiaoyan Zeng Tian He Jun Yin national Key Laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan 430079China

Due to their excellent fluorescence properties and biological function,cyanine dyes have been widely applied in biological *** cyanine(Cy7)dyes,as a type of classic near-infrared(NIR)fluorescent dyes,are considered as one of the effective fluorescent tools in the living organisms due to their good biocompatibility and very low background *** reactions performed in living cells and tissues have developed by leaps and bounds in recent *** NIR fluorescent labeling technique involving cyanine has attracted widespread *** review summarizes their recent application in the field of bioorthogonal imaging,mainly concluding Cy7-type dyes,labeling strategy,bioimaging application,*** expect this work can provide some helps for the studies of NIR bioorthogonal reaction in vivo.

关键词： Fluorescent probes Heptamethine cyanines Bioorthogonal reaction Imaging cell

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A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of general Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

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A Wnt10a-Notch signaling axis controls Hertwig’s epithelial root sheath cell behaviors during root furcation patterning

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international Journal of Oral Science 2024年第3期16卷 425-435页

作者： Kai Sun Miao Yu Jiayu Wang Hu Zhao Haochen Liu Hailan Feng Yang Liu Dong Han Department of Prosthodontics Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Chinese Institute for Brain research BeijingChina

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root ***,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig’s epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains *** this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10a^(fl/fl)mice from post-natal day 0.5(PN0.5)to *** assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10a^(fl/fl)mice at PN2.5 and *** staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10a^(fl/fl)***-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10a^(fl/fl)***,after activation of Notch signaling in K14-Cre;Wnt10a^(fl/fl)molars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially *** together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

关键词： Wnt10a Notch impaired

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Orchestrating seed storage protein and starch accumulation toward overcoming yield–quality trade-off in cereal crops

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Journal of Integrative Plant Biology 2024年第3期66卷 468-483页

作者： Shuanghe Cao Bingyan Liu Daowen Wang Awais Rasheed Lina Xie Xianchun Xia Zhonghu He State Key Laboratory of Crop gene Resources and Breeding/national Wheat Improvement center Institute of Crop SciencesBeijing 100081China College of Agronomy Henan Agricultural UniversityZhengzhou 450002China international Maize and Wheat Improvement center(CIMMYT)China Office Chinese Academy of Agricultural SciencesBeijing 100081China

Achieving high yield and good quality in crops is essential for human food security and ***,there is usually disharmony between yield and *** storage protein(SSP)and starch,the predominant components in cereal grains,determine yield and quality,and their coupled synthesis causes a yield–quality ***,dissection of the underlying regulatory mechanism facilitates simultaneous improvement of yield and ***,we summarize current findings about the synergistic molecular machinery underpinning SSP and starch synthesis in the leading staple cereal crops,including maize,rice and *** further evaluate the functional conservation and differentiation of key regulators and specify feasible research approaches to identify additional regulators and expand *** also present major strategies to leverage resultant information for simultaneous improvement of yield and quality by molecular ***,future perspectives on major challenges are proposed.

关键词： cereal crops grain yield and quality seed storage protein starch synergistic regulation

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Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu Department of Physiology School of MedicineJinan UniversityGuangzhou 510632China Department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Biotherapy center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DGAT2 SGLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

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