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Molecular Therapy: the Journal of the American Society of Gene Therapy最新文献

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Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles. ECO/pRHO-ABCA4自组装纳米颗粒对Stargardt病的非病毒基因治疗
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2020-01-01 DOI: 10.1016/j.ymthe.2019.09.010
Da Sun, Rebecca M. Schur, A. Sears, Songqi Gao, Amita M. Vaidya, Wenyu Sun, A. Maeda, T. Kern, K. Palczewski, Zheng-Rong Lu
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引用次数: 29
The Vascular Disrupting Agent CA4P Improves the Antitumor Efficacy of CAR-T Cells in Preclinical Models of Solid Human Tumors. 血管干扰剂CA4P提高CAR-T细胞在实体人肿瘤临床前模型中的抗肿瘤效果
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2020-01-01 DOI: 10.1016/j.ymthe.2019.10.010
Changwen Deng, Jingjing Zhao, Shixin Zhou, Jiebin Dong, Jixiang Cao, Junshuang Gao, Yun Bai, H. Deng
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引用次数: 31
Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology. shRNA微环的全身外泌体递送可预防帕金森病病理。
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-04 Epub Date: 2019-08-27 DOI: 10.1016/j.ymthe.2019.08.010
María Izco, Javier Blesa, Martin Schleef, Marco Schmeer, Riccardo Porcari, Raya Al-Shawi, Stephan Ellmerich, María de Toro, Chris Gardiner, Yiqi Seow, Alejandro Reinares-Sebastian, Raquel Forcen, J Paul Simons, Vittorio Bellotti, J Mark Cooper, Lydia Alvarez-Erviti

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases.

开发减缓或停止帕金森病进展的新疗法是医疗保健的优先事项。一个关键的病理特征是α -突触核蛋白聚集的存在，越来越多的证据表明α -突触核蛋白的繁殖在疾病进展中起着核心作用。因此，α -突触核蛋白的下调是一个潜在的治疗靶点。作为一种慢性疾病，理想的治疗方法是微创且长期有效。基因表达的敲低具有明确的潜力，α -突触核蛋白特异性sirna已被设计出来；然而，siRNA治疗的疗效受到其短期疗效的限制。为了解决这个问题，我们设计了shRNA微环（shRNA- mcs），具有延长效力的潜力，并使用rvg -外泌体作为特异性递送到大脑的载体。我们使用表达GFP的转基因小鼠对该系统进行了优化，并证明其在大脑中下调GFP蛋白表达的能力长达6周。rvg外泌体用于向α -突触核蛋白预形成原纤维诱导的帕金森病模型提供抗α -突触核蛋白shRNA-MC治疗。该疗法减少了α -突触核蛋白聚集，减少了多巴胺能神经元的损失，改善了临床症状。我们的研究结果证实了rvg外泌体递送的shRNA-MCs在神经退行性疾病的长期治疗中的治疗潜力。
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引用次数: 0
A Cohesin-Mediated Intrachromosomal Loop Drives Oncogenic ROR lncRNA to Accelerate Tumorigenesis. 内聚蛋白介导的染色体内环驱动致癌ROR lncRNA加速肿瘤发生。
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/j.ymthe.2019.07.020
Jiayan Fan, Yangfan Xu, Xu-yang Wen, S. Ge, Renbing Jia, He Zhang, Xianqun Fan
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引用次数: 8
Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine. 抗逆转录病毒药物利匹韦林抑制脑内寨卡病毒感染。
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/j.ymthe.2019.10.006
I. Sariyer, J. Gordon, T. Burdo, Hassen S Wollebo, Eleonora Gianti, Martina Donadoni, A. Bellizzi, S. Cicalese, Regina Loomis, J. Robinson, V. Carnevale, J. Steiner, M. H. Ozdener, Andrew D. Miller, S. Amini, M. Klein, K. Khalili
{"title":"Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine.","authors":"I. Sariyer, J. Gordon, T. Burdo, Hassen S Wollebo, Eleonora Gianti, Martina Donadoni, A. Bellizzi, S. Cicalese, Regina Loomis, J. Robinson, V. Carnevale, J. Steiner, M. H. Ozdener, Andrew D. Miller, S. Amini, M. Klein, K. Khalili","doi":"10.1016/j.ymthe.2019.10.006","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.10.006","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82332034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 18
Systemic Delivery of CRISPR/Cas9 Targeting HPV Oncogenes Is Effective at Eliminating Established Tumors. 靶向HPV癌基因的CRISPR/Cas9系统递送可有效消除已建立的肿瘤
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/j.ymthe.2019.08.012
Luqman Jubair, Sora Fallaha, N. McMillan
{"title":"Systemic Delivery of CRISPR/Cas9 Targeting HPV Oncogenes Is Effective at Eliminating Established Tumors.","authors":"Luqman Jubair, Sora Fallaha, N. McMillan","doi":"10.1016/j.ymthe.2019.08.012","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.08.012","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88924157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 50
Targeted Integration and High-Level Transgene Expression in AAVS1 Transgenic Mice after In Vivo HSC Transduction with HDAd5/35++ Vectors. hdad5 /35++载体体内HSC转导后AAVS1转基因小鼠的靶向整合和高水平转基因表达
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/j.ymthe.2019.08.006
Chang Li, Arpit Mishra, Sucheol Gil, Meng Wang, A. Georgakopoulou, T. Papayannopoulou, R. D. Hawkins, A. Lieber
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引用次数: 29
Fetal Gene Therapy Using a Single Injection of Recombinant AAV9 Rescued SMA Phenotype in Mice. 单次注射重组AAV9挽救小鼠SMA表型的胎儿基因治疗。
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/j.ymthe.2019.08.017
A. Rashnonejad, Gholamhossein Amini Chermahini, Cumhur Gündüz, H. Onay, A. Aykut, B. Durmaz, M. Baka, Q. Su, G. Gao, F. Özkınay
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引用次数: 23
Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles. 设计用于自组装成纳米颗粒的HIV Env免疫原RNA复制子的免疫原性
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-12-01 DOI: 10.1016/J.YMTHE.2019.08.007
M. Melo, E. Porter, Y. Zhang, Murillo Silva, Na Li, Brian S. Dobosh, Alessia Liguori, Patrick D. Skog, E. Landais, S. Menis, D. Sok, D. Nemazee, W. Schief, Ron Weiss, D. Irvine
{"title":"Immunogenicity of RNA Replicons Encoding HIV Env Immunogens Designed for Self-Assembly into Nanoparticles.","authors":"M. Melo, E. Porter, Y. Zhang, Murillo Silva, Na Li, Brian S. Dobosh, Alessia Liguori, Patrick D. Skog, E. Landais, S. Menis, D. Sok, D. Nemazee, W. Schief, Ron Weiss, D. Irvine","doi":"10.1016/J.YMTHE.2019.08.007","DOIUrl":"https://doi.org/10.1016/J.YMTHE.2019.08.007","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82012755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 47
DGCR8/ZFAT-AS1 Promotes CDX2 Transcription in a PRC2 Complex-Dependent Manner to Facilitate the Malignant Biological Behavior of Glioma Cells. DGCR8/ZFAT-AS1以PRC2复合物依赖的方式促进CDX2转录，促进胶质瘤细胞的恶性生物学行为。
Molecular Therapy: the Journal of the American Society of Gene Therapy
Pub Date : 2019-11-20 DOI: 10.1016/j.ymthe.2019.11.015
Fangfang Zhang, Xuelei Ruan, Jun Ma, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, S. Shen, Lianqi Shao, Di Wang, Chunqing Yang, H. Cai, Zhen Li, Ziyi Feng, Yixue Xue
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引用次数: 19
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