作者: Baker, Alexander T. ; Humphreys, Ian R. ; Humphreys, Ian R ; Davies, James A. ; Milward, Kate F. ; Baker, Alexander T ; Milward, Kate ; Kerr-Jones, Lauren E ; Badder, Luned M ; Williams, Marta ; Milward, Kate F ; George, Sarah J. ; George, Sarah J ; Badder, Luned M. ; Kerr-Jones, Lauren E. ; Bliss, Carly M ; Parker, Alan L. ; Hulin-Curtis, Sarah L. ; Statkute, Evelina ; Marušková, Mahulena ; Kerstetter, Lucas ; Davies, James A ; Russell, Gabrielle ; Bliss, Carly M. ; Coughlan, Lynda ; Hulin-Curtis, Sarah L ; Stanton, Richard J ; Parker, Alan L ; Stack, Louise ; Stanton, Richard J.

Adenoviruses (Ads) have demonstrated significant success as replication-deficient (RD) viral vectored vaccines, as well as broad potential across gene therapy and cancer therapy. Ad vectors transduce human cells via direct interactions between the viral fiber knob and cell surface receptors, with secondary cellular integrin interactions. Ad receptor usage is diverse across the extensive phylogeny. Commonly studied human Ad serotype 5 (Ad5), and chimpanzee Ad-derived vector "ChAdOx1" in licensed ChAdOx1 nCoV-19 vaccine, both form primary interactions with the coxsackie and adenovirus receptor (CAR), which is expressed on human epithelial cells and erythrocytes. CAR usage is suboptimal for targeted gene delivery to cells with low/negative CAR expression, including human dendritic cells (DCs) and vascular smooth muscle cells (VSMCs). We evaluated the performance of an RD Ad5 vector pseudotyped with the fiber knob of human Ad serotype 49, termed Ad5/49K vector. Ad5/49K demonstrated superior transduction of murine and human DCs over Ad5, which translated into significantly increased T cell immunogenicity when evaluated in a mouse cancer vaccine model using 5T4 tumor-associated antigen. Additionally, Ad5/49K exhibited enhanced transduction of primary human VSMCs. These data highlight the potential of Ad5/49K vector for both vascular gene therapy applications and as a potent vaccine vector.

2020-08-20·JCI Insight

Curative in vivo hematopoietic stem cell gene therapy of murine thalassemia using large regulatory elements.

Article

作者: Pande, Amit ; Yannaki, Evangelia ; Papayannopoulou, Thalia ; Anagnostopoulos, Achilles ; Bashyam, Ashvin ; Georgakopoulou, Aphrodite ; Wang, Hongjie ; Gil, Sucheol ; Li, Chang ; Izsvák, Zsuzsanna ; Lieber, André ; Liu, Zhinan

Recently, we demonstrated that hematopoietic stem/progenitor cell (HSPC) mobilization followed by intravenous injection of integrating, helper-dependent adenovirus HDAd5/35++ vectors resulted in efficient transduction of long-term repopulating cells and disease amelioration in mouse models after in vivo selection of transduced HSPCs. Acute innate toxicity associated with HDAd5/35++ injection was controlled by appropriate prophylaxis, making this approach feasible for clinical translation. Our ultimate goal is to use this technically simple in vivo HSPC transduction approach for gene therapy of thalassemia major or sickle cell disease. A cure of these diseases requires high expression levels of the therapeutic protein (γ- or β-globin), which is difficult to achieve with lentivirus vectors because of their genome size limitation not allowing larger regulatory elements to be accommodated. Here, we capitalized on the 35 kb insert capacity of HDAd5/35++ vectors to demonstrate that transcriptional regulatory regions of the β-globin locus with a total length of 29 kb can efficiently be transferred into HSPCs. The in vivo HSPC transduction resulted in stable γ-globin levels in erythroid cells that conferred a complete cure of murine thalassemia intermedia. Notably, this was achieved with a minimal in vivo HSPC selection regimen.

2008-01-01·CURRENT EYE RESEARCH

Distinctive gene transduction efficiencies of commonly used viral vectors in the retina.

Article

作者: Wu, Xiao-Bing ; Zhang, Sheng-Hai ; Dong, Xiao-Yan ; Wu, Ji-Hong ; Qian-Huang ; Liu, Xin-Jian ; Li, Chuan-Yuan

The transduction efficiency and cell tropism of viral vectors rAAV2/1, rAAV2, Ad5, Ad5/F35, and Lentivirus were evaluated in retina. All viral vectors achieved efficient transduction in living rat retina. However, each vector showed distinctive efficiency in vitro especially for rAAV2/1, which displayed poor transduction in cultured retinal cells. Distinctive cell-specific GFP expression was observed in vivo and in vitro for the same viral vector. The cell-specific tropism was not strictly correlated with the correspondent distribution of viral receptors in retina. These results provided important insights into the selection of appropriate vectors when specific retinal diseases are considered for gene therapy.

100 项与 Ad5/35-HIV vaccine(Yokohama City University) 相关的药物交易

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