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Human Gene Therapy

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https://www.readbyqxmd.com/read/29227172/a-retinal-research-nonprofit-paves-the-way-for-commercializing-gene-therapies
#1
Ben Shaberman
No abstract text is available yet for this article.
December 11, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29216761/efficient-therapeutic-protein-expression-using-retroviral-replicating-vector-with-2a-peptide-in-cancer-models
#2
Andrew Hofacre, Kader Yagiz, Daniel Mendoza, Fernando Lopez Espinoza, Anthony Munday, Cindy Burrascano, Oded Singer, Harry Gruber, Doug Jolly, Amy Lin
Toca 511, a retroviral replicating vector (RRV), uses an internal ribosomal entry site (IRES) to express an optimized yeast cytosine deaminase (yCD2), which converts 5-fluorocytosine to 5-fluorouracil. This configuration is genetically stable in both preclinical mouse models and human clinical trials. However, the use of IRES (~ 600 bp) restricts choices of therapeutic transgenes due to limits in RRV genome size. In this study, we replaced IRES with 2A peptides derived from picornaviruses with or without a GSG linker...
December 7, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29212391/gene-therapy-successfully-delays-degeneration-in-a-mouse-model-of-pde6a-linked-retinitis-pigmentosa-rp-43
#3
Christian Schön, Vithiyanjali Sothilingam, Regine Mühlfriedel, Marina Garcia Garrido, Susanne C Beck, Naoyuki Tanimoto, Bernd Wissinger, François Paquet-Durand, Martin Biel, Stylianos Michalakis, Mathias W Seeliger, Rd-Cure Consortium
Retinitis pigmentosa type 43 (RP43) is a blinding disease caused by mutations in the gene for rod phosphodiesterase 6 alpha (PDE6A). The disease process begins with a dysfunction of rod photoreceptors, subsequently followed by a currently untreatable progressive degeneration of the entire outer retina. Aiming at a curative approach via PDE6A gene supplementation, we developed a novel adeno-associated viral (AAV) vector for expression of the human PDE6A cDNA under control of the human rhodopsin promotor (rAAV8...
December 7, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29212382/gene-supplementation-rescues-rod-function-and-preserves-photoreceptor-and-retinal-morphology-in-dogs-leading-the-way-towards-treating-human-pde6a-retinitis-pigmentosa
#4
Laurence M Occelli, Christian Schön, Mathias W Seeliger, Martin Biel, Stylianos Michalakis, Simon Petersen-Jones, Rd-Cure Consortium
Mutations in the phosphodiesterase 6A gene (PDE6A) result in retinitis pigmentosa type 43 (RP43) and are responsible for about 4% of autosomal recessive RP. There is currently no treatment for this blinding condition. The aim of this project was to use a large animal model to test a gene supplementation viral vector designed to be translated for use in a clinical trial for the treatment of RP43. Seven Pde6a<sup>-/-</sup> puppies were given subretinal injections of an adeno-associated viral vector serotype 2/8 delivering human PDE6A cDNA under control of a short rhodopsin promoter (AAV8-PDE6A)...
December 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29212377/gene-therapy-for-bone-repair-using-human-cells-superior-osteogenic-potential-of-bmp-2-transduced-mesenchymal-stem-cells-derived-from-adipose-tissue-compared-to-bone-marrow
#5
Sofia Bougioukli, Osamu Sugiyama, William Pannell, Brandon Ortega, Matthew Tan, Amy Tang, Robert Yoho, Daniel A Oakes, Jay R Lieberman
Ex vivo regional gene therapy strategies using animal mesenchymal stem cells genetically modified to overexpress osteoinductive growth factors has been successfully used in a variety of animal models to induce both heterotopic and orthotopic bone formation. However, in order to adapt regional gene therapy for clinical applications it is essential to assess the osteogenic capacity of transduced human cells and choose the cell type that demonstrates the best clinical potential. Bone marrow stem cells (BMSC) and adipose-derived stem cells (ASC) were selected in our study for in vitro evaluation, before and after transduction with a lentiviral two-step transcriptional amplification system (TSTA) overexpressing BMP-2 (LV-TSTA-BMP-2) or GFP (LV-TSTA-GFP); cell growth, transduction efficiency, BMP-2 production and osteogenic capacity were assessed...
December 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29207890/artificial-mirnas-reduce-human-mutant-huntingtin-throughout-the-striatum-in-a-transgenic-sheep-model-of-huntington-s-disease
#6
Edith Pfister, Natalie Dinardo, Erica Mondo, Florie Borel, Faith Conroy, Cara Fraser, Gwladys Gernoux, Xin Han, Danjing Hu, Emily Johnson, Lori Kennington, PengPeng Liu, Suzanne Reid, Ellen Sapp, Petr Vodicka, Tim Kuchel, A Jennifer Morton, David Howland, Richard Moser, Miguel Sena-Esteves, Guangping Gao, Christian Mueller, Marian DiFiglia, Neil Aronin
Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT but evidence for their effectiveness and safety in larger animals is lacking. HD transgenic sheep express the full-length human HTT with 73 CAG repeats. We used AAV9 to unilaterally deliver to HD sheep striatum an artificial miRNA targeting exon 48 of the human HTT mRNA under control of two alternative promoters- U6 or CβA...
December 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29207878/cd20-cd19-bispecific-car-t-cells-for-the-treatment-of-b-cell-malignancies
#7
Alexandra Martyniszyn, Ann-Christin Krahl, Maya C André, Andreas A Hombach, Hinrich Abken
The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells which lack the CAR targeted antigen. In this situation a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing also leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T cell activation...
December 5, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29179602/gene-transfer-of-zmapp-antibodies-mediated-by-recombinant-adeno-associated-virus-protects-against-ebola-infections
#8
Marc-André Robert, Nasha Nassoury, Parminder S Chahal, Marie-Hélène Venne, Trina Racine, Xiangguo Qiu, Gary Kobinger, Amine Kamen, Rénald Gilbert, Bruno Gaillet
Vectored delivery of the ZMapp antibody cocktail (c2G4, c4G7 and c13C6) by using recombinant adeno-associated viruses (rAAVs) could be useful for preventive immunization against Ebola virus infections because rAAVs can generate long-term antibody expression. Three rAAVs (serotype 9) encoding chimeric ZMapp antibodies were produced by triple-plasmid transfection up to 10 L-scale in WAVE bioreactors using HEK293 cells grown in suspension/serum-free conditions. Efficacy of AAV-c2G4 via intravenous (IV), intramuscular (IM) and intranasal (IN) routes of administration was evaluated in mice with two different doses of 2...
November 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29179583/oncolytic-viruses-for-tumor-precision-imaging-and-radiotherapy
#9
Zi Jun Wu, Feng R Tang, Zhao-Wu Ma, Xiao-Chun Peng, Ying Xiang, Yanling Zhang, Jingbo Kang, Jiafu Ji, Xiao Q Liu, Xian-Wang Wang, Hong-Wu Xin, Bo X Ren
Dr. Peng et al invented the recombinant adenovirus expressing p53 (rAd-p53, Gendicine) for clinical tumor virotherapy in China in 2003, which is the first clinically approved gene therapy and tumor virotherapy drug in the world. An oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor (Talimogene laherparepvec, T-VEC) was approved for melanoma treatment in the United States in 2015. Since then, oncolytic viruses have been attracting more and more attention in the field of oncology, and may become novel significant modalities of tumor precision imaging and radiotherapy after further improvement...
November 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29179571/the-role-of-basal-cells-in-producing-persistent-lentivirus-mediated-airway-gene-expression
#10
Nigel R Farrow, Martin Donnelley, Patricia Cmielewski, Eugene Roscioli, Nathan Rout-Pitt, Chantelle McIntyre, Ivan Bertoncello, David Parsons
RATIONALE: Cystic Fibrosis (CF) lung disease is an ideal candidate for a genetic therapy. We have previously shown that pre-conditioning with lysophosphatidylcholine (LPC) prior to lentiviral (LV) vector delivery results in long-term in vivo gene expression in the airway epithelium of CF mice. We hypothesise that this outcome is largely due to transduction of airway basal cells that in turn pass the transgene onto their progeny. OBJECTIVES: The aim of these studies was to confirm if the in vivo delivery of a HIV-1 VSV-G pseudotyped LV vector following LPC airway conditioning results in transduction of mouse airway basal cells in situ and if the transgene is passed onto their progeny...
November 27, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29160173/gene-delivery-to-joints-by-intra-articular-injection
#11
Christopher H Evans, Steven Craig Ghivizzani, Paul D Robbins
Most forms of arthritis are incurable, difficult to treat and a major cause of disability in western countries. Better local treatment of arthritis is impaired by the pharmacokinetics of the joint that make it very difficult to deliver drugs to joints at sustained, therapeutic concentrations. This is especially true of biologic drugs, such as proteins and RNA, many of which show great promise in pre-clinical studies. Gene transfer provides a strategy for overcoming this limitation. The basic concept is to deliver cDNAs encoding therapeutic products by direct intra-articular injection, leading to sustained, endogenous synthesis of the gene products within the joint...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29160116/assessment-of-aav-serotype-tropism-in-human-retinal-explants
#12
Luke Aaron Wiley, Erin Burnight, Emily E Kaalberg, Chunhua Jiao, Megan J Riker, Jennifer A Halder, Meagan A Luse, Ian C Han, Stephen R Russell, Elliott H Sohn, Edwin Stone, Budd A Tucker, Robert F Mullins
Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to human retina. In this study, we evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of 7 different adeno-associated viral type 2 (AAV2) serotypes in human retina and retinal pigment epithelium-choroid: AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9, all driving expression of GFP under control of the cytomegalovirus promoter...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29160103/integration-site-analysis-in-gene-therapy-patients-expectations-and-reality
#13
Luca Biasco
Integration site analysis is one of the major tools for addressing the safety of gene therapy clinical protocols based on the use of integrating vectors. Over the past years, the study of viral insertions in gene therapy treated patients has allowed identifying insertional mutagenesis events, evaluating the safety of new viral vector platforms and tracking the in vivo clonal dynamics of genetically engineered cell products. While gene therapy is progressively expanding its impact on a broader area of clinical applications, increasingly more accessible, faster and more reliable safety readouts are required from integration site analysis...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29130354/delivery-of-adeno-associated-viral-vectors-in-adult-mammalian-inner-ear-cell-subtypes-without-auditory-dysfunction
#14
Yong Tao, Mingqian Huang, Yilai Shu, Adam Ruprecht, Hongyang Wang, Yong Tang, Luk H Vandenberghe, Qiuju Wang, Guangping Gao, Wei-Jia Kong, Zheng-Yi Chen
Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in human with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to effectively recover auditory functions in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points whereas in human the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether or not AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damages to the inner ear...
November 12, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28967304/systemic-smad7-gene-therapy-increases-striated-muscle-mass-and-enhances-exercise-capacity-in-a-dose-dependent-manner
#15
Joseph W Maricelli, Yemeserach M Bishaw, Bo Wang, Min Du, Buel D Rodgers
Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated virus (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and, as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to improve systemic muscle function similarly, especially exercise capacity...
November 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28950723/transplantation-of-hepatocyte-growth-factor-modified-dental-pulp-stem-cells-prevents-bone-loss-in-the-early-phase-of-ovariectomy-induced-osteoporosis
#16
Fanxuan Kong, Xuefeng Shi, Fengjun Xiao, Yuefeng Yang, Xiaoyan Zhang, Li-Sheng Wang, Chu-Tse Wu, Hua Wang
Investigations based on mesenchymal stem cells (MSCs) for osteoporosis have attracted attention recently. MSCs can be derived from various tissues, such as bone marrow, adipose, umbilical cord, placenta, and dental pulp. Among these, dental pulp-derived MSCs (DPSCs) and hepatocyte growth factor (HGF)-modified DPSCs (DPSCs-HGF) highly express osteogenic-related genes and have stronger osteogenic differentiation capacities. DPSCs have more benefits in treating osteoporosis. The purpose of this study was to investigate the roles of HGF gene-modified DPSCs in bone regeneration using a mouse model of ovariectomy (OVX)-induced bone loss...
November 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28922955/comparison-of-zinc-finger-nucleases-versus-crispr-specific-nucleases-for-genome-editing-of-the-wiskott-aldrich-syndrome-locus
#17
Alejandra Gutierrez-Guerrero, Sabina Sanchez-Hernandez, Giuseppe Galvani, Javier Pinedo-Gomez, Rocio Martin-Guerra, Almudena Sanchez-Gilabert, Araceli Aguilar-González, Marién Cobo, Philip Gregory, Michael Holmes, Karim Benabdellah, Francisco Martin
Primary immunodeficiencies, including Wiskott-Aldrich syndrome (WAS), are a main target for genome-editing strategies using specific nucleases (SNs) because a small number of corrected hematopoietic stem cells could cure patients. In this work, we have designed various WAS gene-specific CRISPR/Cas9 systems and compared their efficiency and specificity with homodimeric and heterodimeric WAS-specific zinc finger nucleases (ZFNs), using K-562 cells as a cellular model and plasmid nucleofection or integration-deficient lentiviral vectors (IDLVs) for delivery...
October 25, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29061083/immuno-oncology-the-translational-runway-for-gene-therapy
#18
Ludger Weß, Frank Schnieders
Cancer therapy once again is experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing single targets or pathways only. Even the combination of several neo-antigens in cancer vaccines is not sufficient for a successful, lasting tumor eradication. The focus therefore has shifted on the immune systems role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells...
October 23, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29054137/interleukin-35-gene-modified-mesenchymal-stem-cells-protect-concanavalin-a-induced-fulminant-hepatitis-by-decreasing-the-interferon-gamma-level
#19
Wei Wang, Hao Guo, Hongyue Li, Yongjia Yan, Chao Wu, Xiaodong Wang, Xianghui He, Na Zhao
Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells (Treg), playing an important role in the prevention of autoimmune diseases. This study used mesenchymal stem cells (MSCs) as the gene-delivery vehicles for IL-35 gene therapy and investigated their protective effects in Concanavalin A (Con A)-induced autoimmune hepatitis. Results showed that IL-35 gene modified MSCs (IL-35-MSCs) can specifically migrate to the injured liver tissues and significantly narrow the necrosis areas of injured livers...
October 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29037080/esgct-xxv-anniversary-congress-in-collaboration-with-the-german-society-for-gene-therapy-october-17-20-2017-berlin-germany
#20
(no author information available yet)
No abstract text is available yet for this article.
October 16, 2017: Human Gene Therapy
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