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Lentivirus vector therapy

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https://www.readbyqxmd.com/read/28160047/a-novel-inducible-lentiviral-system-for-multi-gene-expression-with-human-hsp70-promoter-and-tetracycline-induced-promoter
#1
Shun Li, Lunkun Ma, Mengting Ou, Jianguo Feng, Yi Liao, Guixue Wang, Liling Tang
Despite lentiviral system's predominance, its ultimate potential for gene therapy has not been fully exploited. Currently, most lentivirus vectors are non-inducible expression system or single-gene-induced system, which limits the extensive application in gene therapy. In this study, we designed a novel lentiviral vector containing HSP70 promoter and TRE promoter. Compared to traditional lentiviral vectors and inducible vectors, our controllable system has many advantages. Firstly, it contains multiple gene or shRNA targets...
February 3, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28135585/genome-wide-profiling-reveals-remarkable-parallels-between-insertion-site-selection-properties-of-the-mlv-retrovirus-and-the-piggybac-transposon-in-primary-human-cd4-t-cells
#2
Andreas Gogol-Döring, Ismahen Ammar, Saumyashree Gupta, Mario Bunse, Csaba Miskey, Wei Chen, Wolfgang Uckert, Thomas F Schulz, Zsuzsanna Izsvák, Zoltán Ivics
The inherent risks associated with vector insertion in gene therapy need to be carefully assessed. We analyzed the genome-wide distributions of Sleeping Beauty (SB) and piggyBac (PB) transposon insertions as well as MLV retrovirus and HIV lentivirus insertions in human CD4(+) T cells with respect to a panel of 40 chromatin states. The distribution of SB transposon insertions displayed the least deviation from random, while the PB transposon and the MLV retrovirus showed unexpected parallels across all chromatin states...
March 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28123488/lentivirus-mediated-rnai-knockdown-of-lmp2a-inhibits-the-growth-of-the-epstein-barr-associated-gastric-carcinoma-cell-line-gt38-in-vitro
#3
Fangjun Wang, Weichang Chen, Pengfei Liu, Jundong Zhou, Bingtuan Liu, Wu Ye, Wenping Wang, Xiuyun Shen
In this study, lentivirus-mediated RNA interference (RNAi) was applied to inhibit latent membrane protein 2A (LMP2A) gene expression, in order to explore the effects of LMP2A silencing on the growth of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) cell line in vitro. Lentivirus-mediated RNAi technology was employed to specifically knock down the LMP2A gene in the EBV-positive gastric carcinoma cell line GT38. After infection, reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry and colony formation assays were conducted to evaluate the expression of LMP2A and the biological behavior of the GT38 cell line in vitro...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27999194/radiation-induced-sod2-overexpression-sensitizes-colorectal-cancer-to-radiation-while-protecting-normal-tissue
#4
Zhiqiang Zhang, Jinyi Lang, Zhi Cao, Rong Li, Xingyong Wang, Weidong Wang
This study investigated whether radiation-induced overexpression of superoxide dismutase 2 (SOD2) exerts radio-sensitizing effects on tumor cells while having radio-protective effects on normal cells during radio-activated gene therapy for human colorectal cancer. A chimeric promoter, C9BC, was generated by directly linking nine tandem CArG boxes to a CMV basic promoter, after which lentiviral vectors containing GFP and SOD2 gene driven by the C9BC promoter were constructed. Stably transfected HT-29 colorectal cancer cells and CCD 841 CoN normal colorectal cells were irradiated to a dose of 6-Gy, and cell proliferation and apoptosis were observed...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27993351/mesenchymal-stem-cells-overexpressing-il-35-effectively-inhibit-cd4-t-cell-function
#5
Na Zhao, Hongyue Li, Yongjia Yan, Ruoyu Jiang, Xianghui He
Mesenchymal stem cells (MSCs) have recently emerged as promising candidates for cell-based immune tolerance therapy. 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. In this study, we isolated adipose tissue-derived MSCs, a good vehicle for cell therapy, which were transfected with a lentivirus vector for the overexpression of the therapeutic murine IL-35 gene...
December 8, 2016: Cellular Immunology
https://www.readbyqxmd.com/read/27987502/-effect-of-type-1-sphingosine-1-phosphate-receptor-sirna-on-human-salivary-gland-cells
#6
Q Li, Z F Chang, G A Yang, C Y Pang, Y F Wang
OBJECTIVE: To construct sphingosine 1-phosphate receptor-1 (S1P1)-small interfering RNA (siRNA) lentiviral vectors and infect human salivary gland cells (HSG), and to investigate its possible therapy on Sjogren's syndrome. METHODS: HSG cells were divided into blank group, empty vector group, scramble-siRNA group and S1P1-siRNA group. The lentiviral vectors expressing siRNA against S1P1 and the pLL3.7 were respectively transfected into 293T cells with pMD2.G, pMDL g/p RRE, pRSV-REV to produce virus, and then infect HSG cells...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27933309/impact-of-age-and-vector-construct-on-striatal-and-nigral-transgene-expression
#7
Nicole K Polinski, Fredric P Manfredsson, Matthew J Benskey, D Luke Fischer, Christopher J Kemp, Kathy Steece-Collier, Ivette M Sandoval, Katrina L Paumier, Caryl E Sortwell
Therapeutic protein delivery using viral vectors has shown promise in preclinical models of Parkinson's disease (PD) but clinical trial success remains elusive. This may partially be due to a failure to include advanced age as a covariate despite aging being the primary risk factor for PD. We investigated transgene expression following intracerebral injections of recombinant adeno-associated virus pseudotypes 2/2 (rAAV2/2), 2/5 (rAAV2/5), 2/9 (rAAV2/9), and lentivirus (LV) expressing green fluorescent protein (GFP) in aged versus young adult rats...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27931511/myod-overexpressed-equine-adipose-derived-stem-cells-enhanced-myogenic-differentiation-potential
#8
Soo-Eun Sung, Meeyul Hwang, Ah-Young Kim, Eun-Mi Lee, Eun-Joo Lee, Su-Kyeong Hwang, Shin-Yoon Kim, Hong-Kyun Kim, Kyu-Shik Jeong
Mesenchymal stem cells could potentially be used in the clinical treatment of muscle disorders and muscle regeneration. Adipose-derived stem cells (ADSCs) can be easily isolated from adipose tissue, as opposed to stem cells of other tissues. We believe that cell therapy using ADSCs could be applied to muscle disorders in horses and other species. We sought to improve the myogenic differentiation potential of equine ADSCs (eqADSCs) using a MyoD lentiviral vector. MyoD lentiviruses were transduced into eqADSCs and selected using puromycin...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930352/mir-590-promotes-transdifferentiation-of-porcine-and-human-fibroblasts-toward-a-cardiomyocyte-like-fate-by-directly-repressing-specificity-protein-1
#9
Vivek P Singh, Megumi Mathison, Vivekkumar Patel, Deepthi Sanagasetti, Brian W Gibson, Jianchang Yang, Todd K Rosengart
BACKGROUND: Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies. METHODS AND RESULTS: Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 (GMT); Hand2 (H), Myocardin (My), or microRNA (miR)-590 were administered to rat, porcine, and human cardiac fibroblasts in vitro...
November 10, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27891535/gene-therapy-for-hemoglobin-disorders-a-mini-review
#10
Parul Rai, Punam Malik
Gene therapy by either gene insertion or editing is an exciting curative therapeutic option for monogenic hemoglobin disorders like sickle cell disease and β-thalassemia. The safety and efficacy of gene transfer techniques has markedly improved with the use of lentivirus vectors. The clinical translation of this technology has met with good success, although key limitations include number of engraftable transduced hematopoietic stem cells and adequate transgene expression that results in complete correction of β0 thalassemia major...
2016: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/27889981/chimeric-trojan-protein-insertion-in-lentiviral-membranes-makes-lentiviruses-susceptible-to-neutralization-by-anti-tetanus-serum-antibodies
#11
Anita Le Heron, Steven Patterson, Rafael J Yáñez-Muñoz, George Dickson
This study describes the initial testing of a novel strategy for neutralization of lentiviruses using the fundamental biology of enveloped viruses' assembly and budding. In the field of gene therapy, viral vector surface proteins have been manipulated in order to redirect host cell specificity by alteration of pseudo-types. This study tested whether known viral pseudo-typing proteins or surface proteins known to be recruited to the human immunodeficiency virus (HIV) envelope could be engineered to carry neutralizing epitopes from another microorganism onto the lentiviral surface...
November 26, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27857058/molecular-imaging-and-cancer-gene-therapy
#12
REVIEW
Z Saadatpour, G Bjorklund, S Chirumbolo, M Alimohammadi, H Ehsani, H Ebrahiminejad, H Pourghadamyari, B Baghaei, H R Mirzaei, A Sahebkar, H Mirzaei, M Keshavarzi
Gene therapy is known as one of the most advanced approaches for therapeutic prospects ranging from tackling genetic diseases to combating cancer. In this approach, different viral and nonviral vector systems such as retrovirus, lentivirus, plasmid and transposon have been designed and employed. These vector systems are designed to target different therapeutic genes in various tissues and cells such as tumor cells. Therefore, detection of the vectors containing therapeutic genes and monitoring of response to the treatment are the main issues that are commonly faced by researchers...
November 18, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27852956/preparation-for-a-first-in-man-lentivirus-trial-in-patients-with-cystic-fibrosis
#13
Eric W F W Alton, Jeffery M Beekman, A Christopher Boyd, June Brand, Marianne S Carlon, Mary M Connolly, Mario Chan, Sinead Conlon, Heather E Davidson, Jane C Davies, Lee A Davies, Johanna F Dekkers, Ann Doherty, Sabrina Gea-Sorli, Deborah R Gill, Uta Griesenbach, Mamoru Hasegawa, Tracy E Higgins, Takashi Hironaka, Laura Hyndman, Gerry McLachlan, Makoto Inoue, Stephen C Hyde, J Alastair Innes, Toby M Maher, Caroline Moran, Cuixiang Meng, Michael C Paul-Smith, Ian A Pringle, Kamila M Pytel, Andrea Rodriguez-Martinez, Alexander C Schmidt, Barbara J Stevenson, Stephanie G Sumner-Jones, Richard Toshner, Shu Tsugumine, Marguerite W Wasowicz, Jie Zhu
We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies...
February 2017: Thorax
https://www.readbyqxmd.com/read/27769802/challenges-of-up-scaling-lentivirus-production-and-processing
#14
REVIEW
Alexandra McCarron, Martin Donnelley, Chantelle McIntyre, David Parsons
Lentiviruses are becoming an increasingly popular choice of gene transfer vehicle for use in the treatment of a variety of genetic and acquired human diseases. As research progresses from basic studies into pre-clinical and clinical phases, there is a growing demand for large volumes of high purity, concentrated vector, and accordingly, the means to produce such quantities. Unlike other viral vectors, lentiviruses are difficult to produce using stable cell lines, therefore transient transfection of adherent cell lines is conventionally used, and this method has proven challenging to up-scale...
December 20, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27756280/lentivirus-mediated-short-hairpin-rna-interference-targeting-tnf-alpha-in-macrophages-inhibits-particle-induced-inflammation-and-osteolysis-in-vitro-and-in-vivo
#15
Chu-Qiang Qin, Dong-Sheng Huang, Chi Zhang, Bin Song, Jian-Bin Huang, Yue Ding
BACKGROUND: Aseptic loosening is a significant impediment to joint implant longevity. Prosthetic wear particles are postulated to play a central role in the onset and progression of periprosthetic osteolysis, leading to aseptic loosening of the prosthesis. METHODS: We investigated the inhibitory effects of a lentivirus-mediated short hairpin RNA that targets the TNF-alpha gene on the particle-induced inflammatory and osteolytic changes via macrophages both in vitro and in vivo...
October 18, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27748828/effect-of-survivin-gene-therapy-via-lentivirus-vector-on-the-course-of-intervertebral-disc-degeneration-in-an-in%C3%A2-vivo-rabbit-model
#16
Bin Yue, Yazhou Lin, Xuexiao Ma, Guoqing Zhang, Bohua Chen
The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5)...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27742844/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#17
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
: : Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
October 14, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27729044/retroviral-vectors-and-transposons-for-stable-gene-therapy-advances-current-challenges-and-perspectives
#18
José Eduardo Vargas, Leonardo Chicaybam, Renato Tetelbom Stein, Amilcar Tanuri, Andrés Delgado-Cañedo, Martin H Bonamino
Gene therapy protocols require robust and long-term gene expression. For two decades, retrovirus family vectors have offered several attractive properties as stable gene-delivery vehicles. These vectors represent a technology with widespread use in basic biology and translational studies that require persistent gene expression for treatment of several monogenic diseases. Immunogenicity and insertional mutagenesis represent the main obstacles to a wider clinical use of these vectors. Efficient and safe non-viral vectors are emerging as a promising alternative and facilitate clinical gene therapy studies...
October 12, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27667178/improvement-of-vascular-function-by-magnetic-nanoparticle-assisted-circumferential-gene-transfer-into-the-native-endothelium
#19
Sarah Vosen, Sarah Rieck, Alexandra Heidsieck, Olga Mykhaylyk, Katrin Zimmermann, Christian Plank, Bernhard Gleich, Alexander Pfeifer, Bernd K Fleischmann, Daniela Wenzel
Gene therapy is a promising approach for chronic disorders that require continuous treatment such as cardiovascular disease. Overexpression of vasoprotective genes has generated encouraging results in animal models, but not in clinical trials. One major problem in humans is the delivery of sufficient amounts of genetic vectors to the endothelium which is impeded by blood flow, whereas prolonged stop-flow conditions impose the risk of ischemia. In the current study we have therefore developed a strategy for the efficient circumferential lentiviral gene transfer in the native endothelium under constant flow conditions...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27611239/lentivirus-mediated-correction-of-artemis-deficient-severe-combined-immunodeficiency
#20
Divya Punwani, Misako Kawahara, Jason Yu, Ukina Sanford, Sushmita Roy, Kiran Patel, Denise A Carbonaro, Andrea D Karlen, Sara Khan, Kenneth Cornetta, Michael Rothe, Axel Schambach, Donald B Kohn, Harry L Malech, R Scott McIvor, Jennifer M Puck, Morton J Cowan
During B and T lymphocyte maturation, V(D)J recombination is initiated by creation of DNA double-strand breaks. Artemis is an exonuclease essential for their subsequent repair by nonhomologous end-joining. Mutations in DCLRE1C, the gene encoding Artemis, cause T(-)B(-)NK(+) severe combined immunodeficiency (ART-SCID) and also confer heightened sensitivity to ionizing radiation and alkylating chemotherapy. Although allogeneic hematopoietic cell transplantation can treat ART-SCID, conditioning regimens are poorly tolerated, leading to early mortality and/or late complications, including short stature, endocrinopathies, and dental aplasia...
January 2017: Human Gene Therapy
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