Current gene therapy最新文献

{"title":"Corrigendum to: Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano.","authors":"Chaitra Venugopal, Shobha K, Kiranmai S Rai, Venkata Bharatkumar Pinnelli, Bindu M Kutty, Anandh Dhanushkodi","doi":"10.2174/156652322303230528200022","DOIUrl":"10.2174/156652322303230528200022","url":null,"abstract":"<p><p>In this correction, the Editor in Chief suggested revising the publication of Figures 3 and 8E in the article after the correction in numeric value. Below is the corrected version of the figures [1]. The electronic version of the article can be found in \"Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano\" in the journal Current Gene Therapy, 2018, 18(5), 307-323. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The original article can be found online at: https://www.eurekaselect.com/article/93056.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"243-244"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA-1260b Promotes Breast Cancer Cell Migration and Invasion by Downregulating CCDC134.","authors":"Zhijian Huang,&nbsp;Shijian Zhen,&nbsp;Liangzi Jin,&nbsp;Jian Chen,&nbsp;Yuanyuan Han,&nbsp;Wen Lei,&nbsp;Fuqing Zhang","doi":"10.2174/1566523222666220901112314","DOIUrl":"https://doi.org/10.2174/1566523222666220901112314","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is the most common type of cancer among women worldwide. MiR-1260b has been widely demonstrated to participate in multiple crucial biological functions of cancer tumorigenesis, but its functional effect and mechanism in human breast cancer have not been fully understood.</p><p><strong>Methods: </strong>qRT-PCR was used to detect miR-1260b expression in 29 pairs of breast cancer tissues and normal adjacent tissues. Besides, the expression level of miR-1260b in BRCA cells was also further validated by qRT-PCR. miR-1260b played its role in the prognostic process by using Kaplan-Meier curves. In addition, miR-1260b knockdown and target gene CCDC134 overexpression model was constructed in cell line MDA-MB-231. Transwell migration and invasion assay was performed to analyze the effect of miR-1260b and CCDC134 on the biological function of BRCA cells. TargetScan and miRNAWalk were used to find possible target mRNAs. The relationship between CCDC134 and immune cell surface markers was analyzed using TIMER and database and the XIANTAO platform. GSEA analysis was used to identify possible CCDC134-associated molecular mechanisms and pathways.</p><p><strong>Results: </strong>In the present study, miR-1260b expression was significantly upregulated in human breast cancer tissue and a panel of human breast cancer cell lines, while the secretory protein coiled-coil domain containing 134 (CCDC134) exhibited lower mRNA expression. High expression of miR-1260b was associated with poor overall survival among the patients by KM plot. Knockdown of miR-1260b significantly suppressed breast cancer cell migration and invasion and yielded the opposite result. In addition, overexpression of CCDC134 could inhibit breast cancer migration and invasion, and knockdown yielded the opposite result. There were significant positive correlations of CCDC134 with CD25 (IL2RA), CD80 and CD86. GSEA showed that miR-1260b could function through the MAPK pathway by downregulating CCDC134.</p><p><strong>Conclusion: </strong>Collectively, these results suggested that miR-1260b might be an oncogene of breast cancer and might promote the migration and invasion of BRCA cells by down-regulating its target gene CCDC134 and activating MAPK signaling pathway as well as inhibiting immune function and causing immune escape in human breast cancer.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"60-71"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9141796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of mTOR Expression by siRNA Leads to Cell Cycle Arrest and Apoptosis Induction in MDA-MB-231 Breast Cancer Cells.","authors":"Roja Sahu,&nbsp;Shivesh Jha,&nbsp;Shakti P Pattanayak","doi":"10.2174/1566523223666230329085606","DOIUrl":"https://doi.org/10.2174/1566523223666230329085606","url":null,"abstract":"<p><strong>Background: </strong>Mammary carcinogenesis, being ranked second in cancer-related mortality and the inadequacy of existing chemotherapy advocates the development of a novel treatment approach targeting its molecular signalling. Hyperactivation of mammalian target of rapamycin (mTOR) has a critical role in developing invasive mammary cancer and it can be a potential target.</p><p><strong>Objective: </strong>This experiment was to explore the efficacy of mTOR-specific siRNA on therapeutic targeting of the mTOR gene, assess its proficiency in suppressing in vitro breast cancer and determine underlying molecular mechanisms.</p><p><strong>Methods: </strong>Specific siRNA targeting mTOR was transfected into MDA-MB-231 cells and mTOR downregulation was validated through qRT-PCR and western blot analysis. Cell proliferation was analysed by MTT assay and confocal microscopy. Apoptosis was studied through flow cytometry and S6K, GSK-3β and caspase 3 expression were estimated. Further, the effect of mTOR blockade on cell cycle progression was determined.</p><p><strong>Results: </strong>Following transfection of mTOR-siRNA into the MDA-MB-231 cells, cell viability and apoptosis were examined which indicates that clinically relevant concentration of mTOR-siRNA inhibited cell growth and proliferation and promote apoptosis, resulting from the suppression of mTOR. This leads to the downregulation of mTOR downstream S6K and upregulation of GSK-3β. An increased level of caspase 3 symbolises that the apoptotic activity is mediated through caspasedependent pathway. Further, mTOR downregulation causes cell cycle arrest in G0/G1 phase as observed in the flow cytometry study.</p><p><strong>Conclusion: </strong>With these results, we can conclude that mTOR-siRNA exerts direct 'anti-breast cancer' activity propagated by the S6K-GSK-3β- caspase 3 mediated apoptosis and by inducing cell cycle arrest.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"228-242"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SFXN3 is Associated with Poor Clinical Outcomes and Sensitivity to the Hypomethylating Therapy in Non-M3 Acute Myeloid Leukemia Patients.","authors":"Yuxuan Dong, Fengbo Jin, Jing Wang, Qingsheng Li, Zhenqi Huang, Leiming Xia, Mingzhen Yang","doi":"10.2174/1566523223666230724121515","DOIUrl":"10.2174/1566523223666230724121515","url":null,"abstract":"<p><strong>Background: </strong>DNA hypermethylation plays a critical role in the occurrence and progression of acute myeloid leukemia (AML). The mitochondrial serine transporter, SFXN3, is vital for onecarbon metabolism and DNA methylation. However, the impact of SFXN3 on the occurrence and progression of AML has not been reported yet.</p><p><strong>Objective: </strong>In this study, we hypothesized that SFXN3 indicates a poor prognosis and suggested tailored treatment for AML patients.</p><p><strong>Methods: </strong>We used GEPIA and TCGA repository data to analyze the expression of SFXN3 and its correlation with survival in AML patients. RT-qPCR was used to detect the SFXN3 level in our enrolled AML patients and volunteers. Additionally, Whole Genome Bisulfite Sequencing (WGBS) was used to detect the genomic methylation level in individuals.</p><p><strong>Results: </strong>Through the TCGA and GEPIA databases, we found that SFXN3 was enriched in AML patients, predicting shorter survival. Furthermore, we confirmed that SFXN3 was primarily overexpressed in AML patients, especially non-M3 patients, and that high SFXN3 in non-M3 AML patients was found to be associated with poor outcomes and frequent blast cells. Interestingly, non-M3 AML patients with high SFXN3 levels who received hypomethylating therapy showed a higher CR ratio. Finally, we found that SFXN3 could promote DNA methylation at transcription start sites (TSS) in non-M3 AML patients. These sites were found to be clustered in multiple vital cell functions and frequently accompanied by mutations in DNMT3A and NPM1.</p><p><strong>Conclusion: </strong>In conclusion, SXFN3 plays an important role in the progression and hypermethylation in non-M3 AML patients and could be a potential biomarker for indicating a high CR rate for hypomethylating therapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"410-418"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-based Gene Therapies for Fighting Drug Resistance Mediated by Cancer Stem Cells.","authors":"Masoumeh Eliyasi Dashtaki,&nbsp;Sorayya Ghasemi","doi":"10.2174/1566523222666220831161225","DOIUrl":"https://doi.org/10.2174/1566523222666220831161225","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are cancer-initiating cells found in most tumors and hematological cancers. CSCs are involved in cells progression, recurrence of tumors, and drug resistance. Current therapies have been focused on treating the mass of tumor cells and cannot eradicate the CSCs. CSCs drug-specific targeting is considered as an approach to precisely target these cells. Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) gene-editing systems are making progress and showing promise in the cancer research field. One of the attractive applications of CRISPR/Cas9 as one approach of gene therapy is targeting the critical genes involved in drug resistance and maintenance of CSCs. The synergistic effects of gene editing as a novel gene therapy approach and traditional therapeutic methods, including chemotherapy, can resolve drug resistance challenges and regression of the cancers. This review article considers different aspects of CRISPR/Cas9 ability in the study and targeting of CSCs with the intention to investigate their application in drug resistance.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"41-50"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9195102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGENE.","authors":"Changsheng Li,&nbsp;Hexiao Tang,&nbsp;Zetian Yang,&nbsp;Zheng Tang,&nbsp;Nitao Cheng,&nbsp;Jingyu Huang,&nbsp;Xuefeng Zhou","doi":"10.2174/1566523222666220829140649","DOIUrl":"https://doi.org/10.2174/1566523222666220829140649","url":null,"abstract":"<p><strong>Background: </strong>The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and cavin family genes in ALI.</p><p><strong>Methods: </strong>To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose DeepGENE to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features.</p><p><strong>Results: </strong>Compared with DNN, GBDT, RF and KNN, the AUC of DeepGENE increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI.</p><p><strong>Conclusion: </strong>DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 1","pages":"72-80"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9494103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Vaccines to Improve Immunogenicity and Effectiveness in Cancer Vaccinations: Advancement and Developments.","authors":"Arun Kumar Singh,&nbsp;Rishabha Malviya","doi":"10.2174/1566523223666221219094849","DOIUrl":"https://doi.org/10.2174/1566523223666221219094849","url":null,"abstract":"<p><p>DNA vaccine is a creative and promising method for cancer treatment. As part of cancer immunotherapy, one or more antigen-specific immune responses are triggered or strengthened using DNA vaccines for cancer immunotherapy, which convey one or more genes encoded by tumour antigens to the immune system. Vaccine efficacy may be greatly increased by new delivery routes, the incorporation of molecular active ingredients and immunomodulatory signals, the modification of prime-boost protocols, or the inhibition of immunological checkpoints. It is possible to overcome the self-tolerance of many tumour antigens by using a mix of adaptive immune system and vaccine design strategies to generate protective adaptive immune responses. Both preventative and therapeutic vaccinations are being developed using this technology in several clinical investigations on DNA cancer immunotherapy. This study examines the immunogenicity and efficacy of DNA vaccines for immunotherapy.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"23 3","pages":"170-183"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9753242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of MicroRNA-652 Expression with Radiation Response of Colorectal Cancer: A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy.","authors":"Surajit Pathak,&nbsp;Wen-Jian Meng,&nbsp;Sushmitha Sriramulu,&nbsp;Ganesan Jothimani,&nbsp;Jaganmohan Reddy Jangamreddy,&nbsp;Antara Banerjee,&nbsp;Alagu Theivanai Ganesan,&nbsp;Gunnar Adell,&nbsp;Xueli Zhang,&nbsp;Alexander Sun-Zhang,&nbsp;Hong Zhang,&nbsp;Xiao-Feng Sun","doi":"10.2174/1566523223666230418111613","DOIUrl":"10.2174/1566523223666230418111613","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified <i>microRNA-652 (miR-652)</i> value on radiotherapy response and outcome in rectal cancer patients.</p><p><strong>Methods: </strong><i>miR-652</i> expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of <i>miR-652</i> with biological factors and the prognosis was examined. The biological function of <i>miR-652</i> was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53^+/+ and p53^-/-) were used for in vitro study. The molecular interactions of <i>miR-652</i> and tumor suppressor genes were studied through a computational approach.</p><p><strong>Results: </strong>In RT patients, <i>miR-652</i> expression was significantly decreased in cancers when compared to non-radiotherapy cases (<i>P</i> = 0.002). High <i>miR-652</i> expression in non-RT patients was with increased apoptosis marker (<i>P</i> = 0.036), ATM (<i>P</i> = 0.010), and DNp73 expression (<i>P</i> = 0.009). High <i>miR-652</i> expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation (<i>P</i> = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of <i>miR-652</i> with apoptosis in rectal cancer. <i>miR-652</i> expression in cancers was negatively related to WRAP53 expression (<i>P</i> = 0.022). After <i>miR-652</i> inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53^+/+ cells was significantly increased compared with HCT116 p53^-/- cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable.</p><p><strong>Conclusion: </strong>Our findings suggest the potential value of <i>miR-652</i> expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"356-367"},"PeriodicalIF":3.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9413493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly(rC) binding protein 1 represses the translation of STAT3 through 5' UTR.","authors":"Ziwei Li, Xiaole Wang, R. Jia","doi":"10.2174/1566523222666220511162934","DOIUrl":"https://doi.org/10.2174/1566523222666220511162934","url":null,"abstract":"BACKGROUND\u0000Signal transducer and activator of transcription 3 (STAT3) is an oncogene and frequently overexpressed in cancers. However, the regulatory mechanisms of STAT3 expression are not fully understood. Poly(rC)-binding protein1 (PCBP1) is an RNA-binding protein that regulates mRNA stability, splicing, and translation. PCBP1 is a tumor suppressor and can inhibit the translation of several oncogenic genes.\u0000\u0000\u0000OBJECTIVE\u0000We aimed to understand the regulatory mechanisms of STAT3 expression.\u0000\u0000\u0000METHODS\u0000The 5' UTR or 3' UTR regions of the human STAT3 gene were inserted to the upstream or downstream of the green fluorescent gene (GFP), respectively, which were used as reporter systems to analyze the inhibitory effects of PCBP1 on STAT3 gene expression. The deletion and point mutation in 5' UTR were used to search the essential regulatory sequences of the translation inhibition. The mutations of PCBP1 protein were analyzed in the cBioPortal online service. The effects of mutated PCBP1 proteins on STAT3 expression, cancer cell proliferation and colony formation were analyzed in oral squamous cell carcinoma (OSCC) cell lines.\u0000\u0000\u0000RESULTS\u0000PCBP1 inhibits mRNA translation through a motif in the 5' UTR of STAT3. Moreover, we found that two leucine residues (Leu100 and Leu102) of PCBP1 protein are frequently mutated in cancers. These mutations abolished the inhibition function of PCBP1 on STAT3 translation. Surprisingly, in contrast to wild-type PCBP1 protein, these mutations can promote the growth and colony formation of cancer cells.\u0000\u0000\u0000CONCLUSION\u0000Overall, we demonstrate that PCBP1 can inhibit the expression of STAT3 through its 5' UTR, and two leucine residues of PCBP1 protein are essential for its functions..","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45448725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hypoxia-regulated retinal pigment epithelium-specific gene therapy vector reduces choroidal neovascularization in a mouse model.","authors":"Yun Yuan, W. Kong, Xiao-Mei Liu, Guo-Hua Shi","doi":"10.2174/1566523222666220405135135","DOIUrl":"https://doi.org/10.2174/1566523222666220405135135","url":null,"abstract":"BACKGROUND\u0000Wet age-related macular degeneration (wAMD) is characterized by the presence of choroidal neovascularization (CNV). Although there are some clinical drugs targeting vascular endothelial growth factor (VEGF) and inhibiting CNV, two major side effects limit their application, including excessive activity of anti-VEGF and frequent intraocular injections. To explore better treatment strategies, researchers developed a hypoxic modulator retinal pigment epithelium (RPE)-specific adeno-associated virus (AAV) vector expressing endostatin to inhibit CNV. However, the mechanism of endostatin is complex. Instead, sFlt-1 can inhibit VEGF-induced angiogenesis through two simple and clear mechanisms, giving rise to sequestration of VEGF and forming inactive heterodimer with the membrane-spanning isoforms of the VEGF receptor Flt-1 and kinase insert domain-containing receptor.\u0000\u0000\u0000OBJECTIVE\u0000In this study, we chose soluble fms-like tyrosine kinase-1 (sFlt-1) as a safer substitute to treat wAMD by inhibiting VEGF-induced angiogenesis.\u0000\u0000\u0000METHODS\u0000AAV2/8-Y733F-REG-RPE-sFlt-1 vector was delivered by intravitreal injection to the eyes of mice. AAV2/8-Y733F vector is a mutant of AAV2/8 vector, and REG-RPE promoter is a hypoxia-regulated RPE-specific promoter. Two animal models were used to evaluate the function of the vector.\u0000\u0000\u0000RESULTS\u0000In the cobalt chloride-induced hypoxia model, the results demonstrated that AAV2/8-Y733F-REG-RPE-sFlt-1 vector induced the expression of sFlt-1 gene in RPE cells through hypoxia. In the laser-induced CNV model, the results demonstrated that AAV2/8-Y733F-REG-RPE-sFlt-1 vector reduced laser-induced CNV.\u0000\u0000\u0000CONCLUSIONS\u0000Hypoxia regulated, RPE-specific AAV vector-mediated sFlt-1 gene is a hypoxia-regulated antiangiogenic vector for wAMD.","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48642831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}