Gene Therapy最新文献_第2页

BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target. BRD9 通过 CST1 上调和与 FOXP1 的相互作用，通过 PI3K/AKT 通路促进胆囊癌的进展，是一个治疗靶点。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-21 DOI: 10.1038/s41434-024-00488-4

Jing Qiang, Cheng Zhao, Liu-Qing Shi, Si-Rui Sun, Hua-Kai Wang, Shi-Lei Liu, Zi-Yi Yang, Ping Dong, Shan-Shan Xiang, Jian-Dong Wang, Yi-Jun Shu

{"title":"BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target.","authors":"Jing Qiang, Cheng Zhao, Liu-Qing Shi, Si-Rui Sun, Hua-Kai Wang, Shi-Lei Liu, Zi-Yi Yang, Ping Dong, Shan-Shan Xiang, Jian-Dong Wang, Yi-Jun Shu","doi":"10.1038/s41434-024-00488-4","DOIUrl":"https://doi.org/10.1038/s41434-024-00488-4","url":null,"abstract":"Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa. 更正：在多种视网膜色素变性模型中，Nr2e3 是一种能挽救视网膜变性并促进平衡的遗传修饰因子。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-18 DOI: 10.1038/s41434-024-00482-w

Sujun Li, Shyamtanu Datta, Emily Brabbit, Zoe Love, Victoria Woytowicz, Kyle Flattery, Jessica Capri, Katie Yao, Siqi Wu, Michael Imboden, Arun Upadhyay, Rasappa Arumugham, Wallace B Thoreson, Margaret M DeAngelis, Neena B Haider

引用次数: 0

Activated factor X delivered by adeno-associated virus significantly inhibited bleeding and alleviated hemophilic synovitis in hemophilic mice 通过腺相关病毒递送的活化 X 因子可显著抑制血友病小鼠出血并缓解血友病滑膜炎

IF 5.1 3区医学

Gene Therapy Pub Date : 2024-09-10 DOI: 10.1038/s41434-024-00479-5

Feixu Zhang, Xinyue Zhou, Baolai Hua, Xinyi He, Zhanao Li, Xiao Xiao, Xia Wu

引用次数: 0

Retraction Note: Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-κB signaling pathway by regulating CCL4 in osteoarthritis. 撤稿说明：抑制microRNA-495可通过调节骨关节炎中的CCL4，激活NF-κB信号通路，从而抑制软骨细胞凋亡。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-09 DOI: 10.1038/s41434-024-00475-9

Da-Wei Yang, Gui-Bin Qian, Ming-Jiu Jiang, Peng Wang, Kun-Zheng Wang

引用次数: 0

Retraction Note: miR-503-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-A. 撤稿说明：miR-503-5p 通过直接下调 VEGF-A 抑制结肠癌肿瘤发生、血管生成和淋巴管生成。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-06 DOI: 10.1038/s41434-024-00486-6

Linlin Wei, Chaonan Sun, Yaotian Zhang, Ning Han, Shichen Sun

引用次数: 0

AAV dose-dependent transduction efficiency in retinal ganglion cells and functional efficacy of optogenetic vision restoration. 视网膜神经节细胞中 AAV 的剂量依赖性转导效率和光遗传学视力恢复的功能效果。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-05 DOI: 10.1038/s41434-024-00485-7

Qi Lu, Anna Wright, Zhuo-Hua Pan

{"title":"AAV dose-dependent transduction efficiency in retinal ganglion cells and functional efficacy of optogenetic vision restoration.","authors":"Qi Lu, Anna Wright, Zhuo-Hua Pan","doi":"10.1038/s41434-024-00485-7","DOIUrl":"https://doi.org/10.1038/s41434-024-00485-7","url":null,"abstract":"Optogenetics is a promising approach for restoring vision to the blind after photoreceptor degeneration. The ability to restore vision through AAV-mediated delivery of light-sensitive proteins, especially channelrhodopsins, into retinal ganglion cells has been extensively demonstrated in animal models. For clinical application, knowledge of viral dose-dependent functional efficacy is desired. In this study, using a triple-knockout blind mouse model and a highly light-sensitive channelrhodopsin variant, we evaluated viral dose-dependent vision restoration through retinal ganglion cell expression by using optomotor behavioral assays. Our results show that both the restored light sensitivity and visual acuity reached peak levels at a medial viral dose of 108 vg. With increasing dose, transduction efficiency continued to increase while protein expression peaked at the dose of ~109 vg and declined at higher doses. Also, a significant increase in retinal gliosis and inflammatory responses started at the dose of ~109 vg, and a marked increase was observed at the dose of ~1010. These results provide valuable insights into viral dose design for clinical studies.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/Cas9-mediated exon skipping to restore premature translation termination in a DFNB4 mouse model. CRISPR/Cas9介导的外显子跳接可恢复 DFNB4 小鼠模型的过早翻译终止。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-04 DOI: 10.1038/s41434-024-00483-9

Chun-Ying Huang, Yi-Hsiu Tsai, Yi-Fen Cheng, Peng-Yu Wu, Yu-Chi Chuang, Po-Yuan Huang, Jai-Shin Liu, Chen-Chi Wu, Yen-Fu Cheng

{"title":"CRISPR/Cas9-mediated exon skipping to restore premature translation termination in a DFNB4 mouse model.","authors":"Chun-Ying Huang, Yi-Hsiu Tsai, Yi-Fen Cheng, Peng-Yu Wu, Yu-Chi Chuang, Po-Yuan Huang, Jai-Shin Liu, Chen-Chi Wu, Yen-Fu Cheng","doi":"10.1038/s41434-024-00483-9","DOIUrl":"https://doi.org/10.1038/s41434-024-00483-9","url":null,"abstract":"SLC26A4 encodes pendrin, a crucial anion exchanger essential for maintaining hearing function. Mutations in SLC26A4, including the prevalent c.919-2 A > G splice-site mutation among East Asian individuals, can disrupt inner ear electrolyte balance, leading to syndromic and non-syndromic hearing loss, such as Pendred syndrome and DFNB4. To explore potential therapeutic strategies, we utilized CRISPR/Cas9-mediated exon skipping to create a Slc26a4∆E8+E9/∆E8+E9 mouse model. We assessed pendrin expression in the inner ear and evaluated vestibular and auditory functions. The Slc26a4∆E8+E9/∆E8+E9 mice demonstrated reframed pendrin in the inner ear and normal vestibular functions, contrasting with severely abnormal vestibular functions observed in the Slc26a4 c.919-2 A > G splicing mutation mouse model. However, despite these molecular achievements, hearing function did not show the expected improvement, consistent with observed pathology, including cochlear hair cell loss and elevated hearing thresholds. Consequently, our findings highlight the necessity for alternative genetic editing strategies to address hearing loss caused by the SLC26A4 c.919-2 A > G mutation.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intravesical nerve growth factor antisense therapy for bladder hypersensitivity induced by psychological stress. 膀胱内神经生长因子反义疗法治疗心理压力引起的膀胱超敏反应。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-09-03 DOI: 10.1038/s41434-024-00484-8

Tetsuichi Saito, Pradeep Tyagi, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka, Naoki Yoshimura

{"title":"Intravesical nerve growth factor antisense therapy for bladder hypersensitivity induced by psychological stress.","authors":"Tetsuichi Saito, Pradeep Tyagi, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka, Naoki Yoshimura","doi":"10.1038/s41434-024-00484-8","DOIUrl":"10.1038/s41434-024-00484-8","url":null,"abstract":"This study assessed the relationship between NGF expression in the bladder and bladder hypersensitivity caused by psychological stress using water avoidance stress (WAS) in rats by modulating the NGF expression using intravesical liposome-complexed NGF antisense oligonucleotide (OND) therapy on WAS-induced bladder dysfunction. Female Wistar rats were divided into control and WAS groups, the latter of which received WAS sessions for 10 days with or without the OND pretreatment. Rats underwent cystometry with or without intravesical application of low-dose protamine sulfate (LD-PS), or pain behavior measurements after LD-PS application. After functional evaluations, the bladder was harvested for histology and molecular studies. WAS rats with or without LD-PS showed shortened intercontraction intervals and increased pain behaviors compared to control rats, which was improved by OND-treatment. Histological studies revealed that LD-PS provoked urothelial exfoliation in WAS rats. Compared to controls, protein assay showed increased NGF levels, and RT-PCR showed increases of TRPV1 and TRPA1 and a decrease in Cx43 in WAS rat bladders, which were improved by OND-treatment. WAS caused bladder hypersensitivity, which was improved by NGF antisense OND treatment. NGF upregulation in the bladder may be a therapeutic target for the treatment of psychological stress-induced bladder dysfunction.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: AAV2-VEGF-B gene therapy failed to induce angiogenesis in ischemic porcine myocardium due to inflammatory responses. 更正：由于炎症反应，AAV2-VEGF-B 基因疗法未能诱导缺血猪心肌的血管生成。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-26 DOI: 10.1038/s41434-024-00481-x

Henna Korpela, Jaakko Lampela, Jonna Airaksinen, Niko Järveläinen, Satu Siimes, Kaisa Valli, Tiina Nieminen, Minttu Turunen, Maria Grönman, Antti Saraste, Juhani Knuuti, Mikko Hakulinen, Pekka Poutiainen, Vesa Kärjä, Jussi Nurro, Seppo Ylä-Herttuala

引用次数: 0

Lentiviral vector gene therapy and CFTR modulators show comparable effectiveness in cystic fibrosis rat airway models. 慢病毒载体基因疗法和 CFTR 调节剂在囊性纤维化大鼠气道模型中显示出相当的疗效。

IF 4.6 3区医学

Gene Therapy Pub Date : 2024-08-25 DOI: 10.1038/s41434-024-00480-y

Alexandra McCarron, Kak-Ming Ling, Samuel T Montgomery, Kelly M Martinovich, Patricia Cmielewski, Nathan Rout-Pitt, Anthony Kicic, David Parsons, Martin Donnelley

{"title":"Lentiviral vector gene therapy and CFTR modulators show comparable effectiveness in cystic fibrosis rat airway models.","authors":"Alexandra McCarron, Kak-Ming Ling, Samuel T Montgomery, Kelly M Martinovich, Patricia Cmielewski, Nathan Rout-Pitt, Anthony Kicic, David Parsons, Martin Donnelley","doi":"10.1038/s41434-024-00480-y","DOIUrl":"https://doi.org/10.1038/s41434-024-00480-y","url":null,"abstract":"Mutation-agnostic treatments such as airway gene therapy have the potential to treat any individual with cystic fibrosis (CF), irrespective of their CF transmembrane conductance regulator (CFTR) gene variants. The aim of this study was to employ two CF rat models, Phe508del and CFTR knockout (KO), to assess the comparative effectiveness of CFTR modulators and lentiviral (LV) vector-mediated gene therapy. Cells were isolated from the tracheas of rats and used to establish air-liquid interface (ALI) cultures. Phe508del rat ALIs were treated with the modulator combination, elexacaftor-tezacaftor-ivacaftor (ETI), and separate groups of Phe508del and KO tracheal epithelial cells were treated with LV-CFTR followed by differentiation at ALI. Ussing chamber measurements were performed to assess CFTR function. ETI-treated Phe508del ALI cultures demonstrated CFTR function that was 59% of wild-type level, while gene-addition therapy restored Phe508del to 68% and KO to 47% of wild-type level, respectively. Our findings show that rat Phe508del-CFTR protein can be successfully rescued with ETI treatment, and that CFTR gene-addition therapy provides significant CFTR correction in Phe508del and KO ALI cultures to levels that were comparable to ETI. These findings highlight the potential of an LV vector-based gene therapy for the treatment of CF lung disease.","PeriodicalId":12699,"journal":{"name":"Gene Therapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0