Molecular therapy : the journal of the American Society of Gene Therapy最新文献

{"title":"Retraction Notice to: Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma Cells.","authors":"Hao Teng, Ping Wang, Yixue Xue, Xiaobai Liu, Jun Ma, Heng Cai, Zhuo Xi, Zhen Li, Yunhui Liu","doi":"10.1016/j.ymthe.2022.03.019","DOIUrl":"https://doi.org/10.1016/j.ymthe.2022.03.019","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"2638"},"PeriodicalIF":12.4,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263216/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice to: Exosome-Derived miR-130a Activates Angiogenesis in Gastric Cancer by Targeting C-MYB in Vascular Endothelial Cells.","authors":"Haiou Yang, Haiyang Zhang, Shaohua Ge, Tao Ning, Ming Bai, Jialu Li, Shuang Li, Wu Sun, Ting Deng, Le Zhang, Guoguang Ying, Yi Ba","doi":"10.1016/j.ymthe.2022.03.020","DOIUrl":"https://doi.org/10.1016/j.ymthe.2022.03.020","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"2637"},"PeriodicalIF":12.4,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263250/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40478639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization with a versatile adenovirus-inspired multimerization platform.","authors":"Christopher Chevillard,&nbsp;Axelle Amen,&nbsp;Solène Besson,&nbsp;Dalil Hannani,&nbsp;Isabelle Bally,&nbsp;Valentin Dettling,&nbsp;Evelyne Gout,&nbsp;Christophe J Moreau,&nbsp;Marlyse Buisson,&nbsp;Salomé Gallet,&nbsp;Daphna Fenel,&nbsp;Emilie Vassal-Stermann,&nbsp;Guy Schoehn,&nbsp;Pascal Poignard,&nbsp;Marie-Claire Dagher,&nbsp;Pascal Fender","doi":"10.1016/j.ymthe.2022.02.011","DOIUrl":"https://doi.org/10.1016/j.ymthe.2022.02.011","url":null,"abstract":"<p><p>Virus-like particles (VLPs) are highly suited platforms for protein-based vaccines. In the present work, we adapted a previously designed non-infectious adenovirus-inspired 60-mer dodecahedric VLP (ADDomer) to display a multimeric array of large antigens through a SpyTag/SpyCatcher system. To validate the platform as a potential COVID-19 vaccine approach, we decorated the newly designed VLP with the glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryoelectron microscopy structure revealed that up to 60 copies of this antigenic domain could be bound on a single ADDomer particle, with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated VLPs already showed a significant specific humoral response following prime vaccination, greatly reinforced by a single boost. Neutralization assays with SARS-CoV-2 spike pseudo-typed virus demonstrated the elicitation of strong neutralization titers, superior to those of COVID-19 convalescent patients. Notably, the presence of pre-existing immunity against the adenoviral-derived particles did not hamper the immune response against the antigen displayed on its surface. This plug and play vaccine platform represents a promising new highly versatile tool to combat emergent pathogens.</p>","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"1913-1925"},"PeriodicalIF":12.4,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/ba/main.PMC8828441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39913094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models.","authors":"Giulietta Maruggi,&nbsp;Corey P Mallett,&nbsp;Jason W Westerbeck,&nbsp;Tiffany Chen,&nbsp;Giuseppe Lofano,&nbsp;Kristian Friedrich,&nbsp;Lin Qu,&nbsp;Jennifer Tong Sun,&nbsp;Josie McAuliffe,&nbsp;Amey Kanitkar,&nbsp;Kathryn T Arrildt,&nbsp;Kai-Fen Wang,&nbsp;Ian McBee,&nbsp;Deborah McCoy,&nbsp;Rebecca Terry,&nbsp;Alison Rowles,&nbsp;Maia Araujo Abrahim,&nbsp;Michael A Ringenberg,&nbsp;Malcolm J Gains,&nbsp;Catherine Spickler,&nbsp;Xuping Xie,&nbsp;Jing Zou,&nbsp;Pei-Yong Shi,&nbsp;Taru Dutt,&nbsp;Marcela Henao-Tamayo,&nbsp;Izabela Ragan,&nbsp;Richard A Bowen,&nbsp;Russell Johnson,&nbsp;Sandra Nuti,&nbsp;Kate Luisi,&nbsp;Jeffrey B Ulmer,&nbsp;Ann-Muriel Steff,&nbsp;Rashmi Jalah,&nbsp;Sylvie Bertholet,&nbsp;Alan H Stokes,&nbsp;Dong Yu","doi":"10.1016/j.ymthe.2022.01.001","DOIUrl":"https://doi.org/10.1016/j.ymthe.2022.01.001","url":null,"abstract":"<p><p>RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans, and the technology is being leveraged for rapid emergency response. In this report, we assessed immunogenicity and, for the first time, toxicity, biodistribution, and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion-stabilized spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNPs). In mice, one immunization with the SAM vaccine elicited a robust spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to phase 1 clinical evaluation (NCT04758962).</p>","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"1897-1912"},"PeriodicalIF":12.4,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/30/main.PMC8721936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies.","authors":"Serdar Durdagi,&nbsp;Timucin Avsar,&nbsp;Muge Didem Orhan,&nbsp;Muge Serhatli,&nbsp;Bertan Koray Balcioglu,&nbsp;Hasan Umit Ozturk,&nbsp;Alisan Kayabolen,&nbsp;Yuksel Cetin,&nbsp;Seyma Aydinlik,&nbsp;Tugba Bagci-Onder,&nbsp;Saban Tekin,&nbsp;Hasan Demirci,&nbsp;Mustafa Guzel,&nbsp;Atilla Akdemir,&nbsp;Seyma Calis,&nbsp;Lalehan Oktay,&nbsp;Ilayda Tolu,&nbsp;Yasar Enes Butun,&nbsp;Ece Erdemoglu,&nbsp;Alpsu Olkan,&nbsp;Nurettin Tokay,&nbsp;Şeyma Işık,&nbsp;Aysenur Ozcan,&nbsp;Elif Acar,&nbsp;Sehriban Buyukkilic,&nbsp;Yesim Yumak","doi":"10.1016/j.ymthe.2021.10.014","DOIUrl":"https://doi.org/10.1016/j.ymthe.2021.10.014","url":null,"abstract":"<p><p>Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).</p>","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"963-974"},"PeriodicalIF":12.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39541111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Therapy Restores Balance and Auditory Functions in a Mouse Model of Usher Syndrome.","authors":"Kevin Isgrig,&nbsp;Jack W Shteamer,&nbsp;Inna A Belyantseva,&nbsp;Meghan C Drummond,&nbsp;Tracy S Fitzgerald,&nbsp;Sarath Vijayakumar,&nbsp;Sherri M Jones,&nbsp;Andrew J Griffith,&nbsp;Thomas B Friedman,&nbsp;Lisa L Cunningham,&nbsp;Wade W Chien","doi":"10.1016/j.ymthe.2022.01.026","DOIUrl":"https://doi.org/10.1016/j.ymthe.2022.01.026","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"975"},"PeriodicalIF":12.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822160/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39848779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels.","authors":"Chenfei Zhou,&nbsp;Wenfei Wei,&nbsp;Jing Ma,&nbsp;Yang Yang,&nbsp;Luojiao Liang,&nbsp;Yanmei Zhang,&nbsp;Zici Wang,&nbsp;Xiaojing Chen,&nbsp;Lei Huang,&nbsp;Wei Wang,&nbsp;Sha Wu","doi":"10.1016/j.ymthe.2021.12.014","DOIUrl":"https://doi.org/10.1016/j.ymthe.2021.12.014","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"976-977"},"PeriodicalIF":12.4,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/b8/main.PMC8822128.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39645345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dibenzazepine-Loaded Nanoparticles Induce Local Browning of White Adipose Tissue to Counteract Obesity.","authors":"Chunhui Jiang,&nbsp;Mario Alberto Cano-Vega,&nbsp;Feng Yue,&nbsp;Liangju Kuang,&nbsp;Naagarajan Narayanan,&nbsp;Gozde Uzunalli,&nbsp;Madeline P Merkel,&nbsp;Shihuan Kuang,&nbsp;Meng Deng","doi":"10.1016/j.ymthe.2021.11.016","DOIUrl":"https://doi.org/10.1016/j.ymthe.2021.11.016","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"502"},"PeriodicalIF":12.4,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753430/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39795943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice to: miR-639 Expression Is Silenced by DNMT3A-Mediated Hypermethylation and Functions as a Tumor Suppressor in Liver Cancer Cells.","authors":"Jing Xiao,&nbsp;Yankun Liu,&nbsp;Fuxia Wu,&nbsp;Ruiyan Liu,&nbsp;Yongli Xie,&nbsp;Qian Yang,&nbsp;Yufeng Li,&nbsp;Min Liu,&nbsp;Shengping Li,&nbsp;Hua Tang","doi":"10.1016/j.ymthe.2021.11.017","DOIUrl":"https://doi.org/10.1016/j.ymthe.2021.11.017","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"503"},"PeriodicalIF":12.4,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753426/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39778240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNA-Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension.","authors":"Yan Xing,&nbsp;Xiaodong Zheng,&nbsp;Yao Fu,&nbsp;Jing Qi,&nbsp;Minghui Li,&nbsp;Mingfei Ma,&nbsp;Shuang Wang,&nbsp;Shuzhen Li,&nbsp;Daling Zhu","doi":"10.1016/j.ymthe.2021.12.009","DOIUrl":"https://doi.org/10.1016/j.ymthe.2021.12.009","url":null,"abstract":"","PeriodicalId":519519,"journal":{"name":"Molecular therapy : the journal of the American Society of Gene Therapy","volume":" ","pages":"501"},"PeriodicalIF":12.4,"publicationDate":"2022-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8753513/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39819771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}