Pub Date : 2019-11-16DOI: 10.1016/j.ymthe.2019.11.012
T. Taghian, M. Marosfoi, A. Puri, O. Cataltepe, R. King, E. Diffie, Anne S Maguire, Douglas R. Martin, Deborah Fernau, A. Batista, T. Kuchel, C. Christou, Raj Perumal, Sundeep Chandra, Paul D. Gamlin, Stephanie Bertrand, T. Flotte, D. McKenna-Yasek, P. Tai, N. Aronin, M. Gounis, M. Sena-Esteves, H. Gray-Edwards
{"title":"A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.","authors":"T. Taghian, M. Marosfoi, A. Puri, O. Cataltepe, R. King, E. Diffie, Anne S Maguire, Douglas R. Martin, Deborah Fernau, A. Batista, T. Kuchel, C. Christou, Raj Perumal, Sundeep Chandra, Paul D. Gamlin, Stephanie Bertrand, T. Flotte, D. McKenna-Yasek, P. Tai, N. Aronin, M. Gounis, M. Sena-Esteves, H. Gray-Edwards","doi":"10.1016/j.ymthe.2019.11.012","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.11.012","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84802092","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}
Pub Date : 2019-11-13DOI: 10.1182/blood-2019-127754
R. Ishino, Yumi Kawase, T. Kitawaki, N. Sugimoto, Maki Oku, Shumpei Uchida, O. Imataki, A. Matsuoka, T. Taoka, K. Kawakami, T. V. van Kuppevelt, T. Todo, A. Takaori-Kondo, N. Kadowaki
Oncolytic herpes simplex virus type 1 (HSV-1) has been investigated to expand its application to various malignancies. Because hematopoietic cells are resistant to HSV-1, its application to hematological malignancies has been rare. Here, we show that the third generation oncolytic HSV-1, T-01, infected and killed 18 of 26 human cell lines and 8 of 15 primary cells derived from various lineages of hematological malignancies. T-01 replicated at low levels in the cell lines. Viral entry and the oncolytic effect were positively correlated with the expression level of nectin-1 and to a lesser extent 3-O-sulfated heparan sulfate, receptors for glycoprotein D of HSV-1, on tumor cells. Transfection of nectin-1 into nectin-1-negative tumor cells made them susceptible to T-01. The oncolytic effects did not appear to correlate with the expression or phosphorylation of antiviral molecules in the cyclic GMP-AMP (cGAS)-stimulator of interferon genes (STING) and PKR-eIF2α pathways. In an immunocompetent mouse model, intratumoral injection of T-01 into lymphoma induced regression of injected, as well as non-injected, contralateral tumors accompanied by abundant infiltration of antigen-specific CD8+ T cells. These data suggest that intratumoral injection of oncolytic HSV-1 may be applicable to systemic hematological malignancies. Nectin-1 expression may be the most useful biomarker for optimal efficacy.
溶瘤性单纯疱疹病毒1型(HSV-1)已被研究以扩大其在各种恶性肿瘤中的应用。由于造血细胞对HSV-1具有耐药性，因此它在血液恶性肿瘤中的应用很少。在这里，我们发现第三代溶瘤性HSV-1, T-01，感染并杀死26个人类细胞系中的18个和来自各种血液恶性肿瘤谱系的15个原代细胞中的8个。T-01在细胞系中低水平复制。病毒的进入和溶瘤作用与HSV-1的糖蛋白D受体nectin-1和3- o -硫酸肝素在肿瘤细胞上的表达水平呈正相关，在较小程度上与3- o -硫酸化硫酸肝素的表达水平呈正相关。将nectin-1转染到nectin-1阴性的肿瘤细胞中，使其对T-01敏感。溶瘤作用似乎与环状GMP-AMP (cGAS)-干扰素基因刺激因子(STING)和PKR-eIF2α通路中抗病毒分子的表达或磷酸化无关。在具有免疫功能的小鼠模型中，瘤内注射T-01可诱导已注射及未注射的对侧肿瘤消退，并伴有抗原特异性CD8+ T细胞的大量浸润。这些数据提示肿瘤内注射溶瘤性HSV-1可能适用于全身血液系统恶性肿瘤。Nectin-1表达可能是最佳疗效最有用的生物标志物。
{"title":"Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies.","authors":"R. Ishino, Yumi Kawase, T. Kitawaki, N. Sugimoto, Maki Oku, Shumpei Uchida, O. Imataki, A. Matsuoka, T. Taoka, K. Kawakami, T. V. van Kuppevelt, T. Todo, A. Takaori-Kondo, N. Kadowaki","doi":"10.1182/blood-2019-127754","DOIUrl":"https://doi.org/10.1182/blood-2019-127754","url":null,"abstract":"Oncolytic herpes simplex virus type 1 (HSV-1) has been investigated to expand its application to various malignancies. Because hematopoietic cells are resistant to HSV-1, its application to hematological malignancies has been rare. Here, we show that the third generation oncolytic HSV-1, T-01, infected and killed 18 of 26 human cell lines and 8 of 15 primary cells derived from various lineages of hematological malignancies. T-01 replicated at low levels in the cell lines. Viral entry and the oncolytic effect were positively correlated with the expression level of nectin-1 and to a lesser extent 3-O-sulfated heparan sulfate, receptors for glycoprotein D of HSV-1, on tumor cells. Transfection of nectin-1 into nectin-1-negative tumor cells made them susceptible to T-01. The oncolytic effects did not appear to correlate with the expression or phosphorylation of antiviral molecules in the cyclic GMP-AMP (cGAS)-stimulator of interferon genes (STING) and PKR-eIF2α pathways. In an immunocompetent mouse model, intratumoral injection of T-01 into lymphoma induced regression of injected, as well as non-injected, contralateral tumors accompanied by abundant infiltration of antigen-specific CD8+ T cells. These data suggest that intratumoral injection of oncolytic HSV-1 may be applicable to systemic hematological malignancies. Nectin-1 expression may be the most useful biomarker for optimal efficacy.","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90828725","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}
Pub Date : 2019-11-13DOI: 10.1016/j.ymthe.2019.11.005
Amanda M. Dudek, N. Zabaleta, E. Zinn, Sirika Pillay, James R. Zengel, C. Porter, Jennifer Santos Franceschini, Reynette Estelien, J. Carette, Guoling Zhou, L. Vandenberghe
{"title":"GPR108 Is a Highly Conserved AAV Entry Factor.","authors":"Amanda M. Dudek, N. Zabaleta, E. Zinn, Sirika Pillay, James R. Zengel, C. Porter, Jennifer Santos Franceschini, Reynette Estelien, J. Carette, Guoling Zhou, L. Vandenberghe","doi":"10.1016/j.ymthe.2019.11.005","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.11.005","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":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89864094","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}
Pub Date : 2019-11-11DOI: 10.1016/j.ymthe.2019.11.002
S. Chatterjee
{"title":"Efficient Nuclease-free HR by Clade F AAV Requires High MOIs with High Quality Vectors.","authors":"S. Chatterjee","doi":"10.1016/j.ymthe.2019.11.002","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.11.002","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79101884","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}
Pub Date : 2019-11-11DOI: 10.1016/j.ymthe.2019.11.003
G. Rogers, Hsu-Yu Chen, Heidy Morales, P. Cannon
{"title":"Reply to \"Efficient Nuclease-free HR by Clade F AAV Requires High MOIs with High Quality Vectors\".","authors":"G. Rogers, Hsu-Yu Chen, Heidy Morales, P. Cannon","doi":"10.1016/j.ymthe.2019.11.003","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.11.003","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":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75974864","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}
Pub Date : 2019-11-11DOI: 10.1016/j.ymthe.2019.11.004
Amanda M. Dudek, M. Porteus
{"title":"Reply to \"Efficient Nuclease-free HR by Clade F AAV Requires High MOIs with High Quality Vectors\".","authors":"Amanda M. Dudek, M. Porteus","doi":"10.1016/j.ymthe.2019.11.004","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.11.004","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77290942","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}
Pub Date : 2019-11-11DOI: 10.1016/j.ymthe.2019.10.018
J. Dupont, Jianjun Guo, Edith Renaud-Gabardos, K. Poulard, V. Latournerie, M. Lawlor, R. Grange, J. Gray, A. Buj-Bello, M. Childers, D. Mack
{"title":"AAV-Mediated Gene Transfer Restores a Normal Muscle Transcriptome in a Canine Model of X-Linked Myotubular Myopathy.","authors":"J. Dupont, Jianjun Guo, Edith Renaud-Gabardos, K. Poulard, V. Latournerie, M. Lawlor, R. Grange, J. Gray, A. Buj-Bello, M. Childers, D. Mack","doi":"10.1016/j.ymthe.2019.10.018","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.10.018","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75905743","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}
Pub Date : 2019-11-01DOI: 10.1016/J.YMTHE.2019.07.019
Yonghui Zhang, Hailin Zhang, M. Wei, T. Mou, T. Shi, Yanyu Ma, Xinyu Cai, Yunzheng Li, Jie Dong, Jiwu Wei
{"title":"Recombinant Adenovirus Expressing a Soluble Fusion Protein PD-1/CD137L Subverts the Suppression of CD8+ T Cells in HCC.","authors":"Yonghui Zhang, Hailin Zhang, M. Wei, T. Mou, T. Shi, Yanyu Ma, Xinyu Cai, Yunzheng Li, Jie Dong, Jiwu Wei","doi":"10.1016/J.YMTHE.2019.07.019","DOIUrl":"https://doi.org/10.1016/J.YMTHE.2019.07.019","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73196645","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}
Pub Date : 2019-11-01DOI: 10.1016/j.ymthe.2019.07.017
William A. Liguore, J. Domire, Dana Button, Yun Wang, Brett D. Dufour, Sathya Srinivasan, J. McBride
{"title":"AAV-PHP.B Administration Results in a Differential Pattern of CNS Biodistribution in Non-human Primates Compared with Mice.","authors":"William A. Liguore, J. Domire, Dana Button, Yun Wang, Brett D. Dufour, Sathya Srinivasan, J. McBride","doi":"10.1016/j.ymthe.2019.07.017","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.07.017","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77451965","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}
Pub Date : 2019-11-01DOI: 10.1016/j.ymthe.2019.07.012
Y. Echigoya, K. Lim, Dyanna Melo, Bo Bao, Nhu Trieu, Y. Mizobe, R. Maruyama, K. Mamchaoui, J. Tanihata, Y. Aoki, S. Takeda, V. Mouly, W. Duddy, T. Yokota
{"title":"Exons 45-55 Skipping Using Mutation-Tailored Cocktails of Antisense Morpholinos in the DMD Gene.","authors":"Y. Echigoya, K. Lim, Dyanna Melo, Bo Bao, Nhu Trieu, Y. Mizobe, R. Maruyama, K. Mamchaoui, J. Tanihata, Y. Aoki, S. Takeda, V. Mouly, W. Duddy, T. Yokota","doi":"10.1016/j.ymthe.2019.07.012","DOIUrl":"https://doi.org/10.1016/j.ymthe.2019.07.012","url":null,"abstract":"","PeriodicalId":19039,"journal":{"name":"Molecular Therapy: the Journal of the American Society of Gene Therapy","volume":"172 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76257849","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}
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