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https://www.readbyqxmd.com/read/27913727/regulated-complex-assembly-safeguards-the-fidelity-of-sleeping-beauty-transposition
#1
Yongming Wang, Diana Pryputniewicz-Dobrinska, Enikö Éva Nagy, Christopher D Kaufman, Manvendra Singh, Steve Yant, Jichang Wang, Anna Dalda, Mark A Kay, Zoltán Ivics, Zsuzsanna Izsvák
The functional relevance of the inverted repeat structure (IR/DR) in a subgroup of the Tc1/mariner superfamily of transposons has been enigmatic. In contrast to mariner transposition, where a topological filter suppresses single-ended reactions, the IR/DR orchestrates a regulatory mechanism to enforce synapsis of the transposon ends before cleavage by the transposase occurs. This ordered assembly process shepherds primary transposase binding to the inner 12DRs (where cleavage does not occur), followed by capture of the 12DR of the other transposon end...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27898092/transposon-mediated-generation-of-cellular-and-mouse-models-of-splicing-mutations-to-assess-the-efficacy-of-snrna-based-therapeutics
#2
Elena Barbon, Mattia Ferrarese, Laetitia van Wittenberghe, Peggy Sanatine, Giuseppe Ronzitti, Fanny Collaud, Pasqualina Colella, Mirko Pinotti, Federico Mingozzi
Disease-causing splicing mutations can be rescued by variants of the U1 small nuclear RNA (U1snRNAs). However, the evaluation of the efficacy and safety of modified U1snRNAs as therapeutic tools is limited by the availability of cellular and animal models specific for a given mutation. Hence, we exploited the hyperactive Sleeping Beauty transposon system (SB100X) to integrate human factor IX (hFIX) minigenes into genomic DNA in vitro and in vivo. We generated stable HEK293 cell lines and C57BL/6 mice harboring splicing-competent hFIX minigenes either wild type (SChFIX-wt) or mutated (SChFIXex5-2C)...
November 29, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27849617/tethered-il-15-augments-antitumor-activity-and-promotes-a-stem-cell-memory-subset-in-tumor-specific-t-cells
#3
Lenka V Hurton, Harjeet Singh, Amer M Najjar, Kirsten C Switzer, Tiejuan Mi, Sourindra Maiti, Simon Olivares, Brian Rabinovich, Helen Huls, Marie-Andrée Forget, Vrushali Datar, Partow Kebriaei, Dean A Lee, Richard E Champlin, Laurence J N Cooper
Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27834306/citation-context-and-impact-of-sleeping-beauties-in-paediatric-research
#4
REVIEW
Jernej Završnik, Peter Kokol, Stefano Del Torso, Helena Blažun Vošner
OBJECTIVES: 'Sleeping beauties', i.e. publications that are not cited for a long while, present interesting findings in science. This study analysed the citation trends of sleeping beauties in paediatric research. METHODS: The study used bibliometric software to analyse the papers citing sleeping beauties in paediatric research, to understand the context in which paediatric sleeping beauties were finally cited and the impact of these sleeping beauties on paediatric research...
November 10, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27832434/monitoring-of-venus-transgenic-cell-migration-during-pregnancy-in-non-transgenic-rabbits
#5
N Lipták, O I Hoffmann, A Kerekes, G Iski, D Ernszt, K Kvell, L Hiripi, Z Bősze
Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system...
November 10, 2016: Transgenic Research
https://www.readbyqxmd.com/read/27825448/dormancy-illuminating-how-a-microbial-sleeping-beauty-awakens
#6
R Gary Sawers
Nitrogen limitation induces dormancy in the cyanobacterium Synechocystis. During dormancy, the bacterium neither photosynthesizes nor divides, yet it maintains low-level metabolic activity. A new study shows how provision of a nitrogen source initiates a regimented genetic program that initially kick-starts metabolism and ultimately photosynthesis.
November 7, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27822155/sleeping-beauties-in-pediatrics
#7
Jernej Završnik, Peter Kokol
Sleeping beauties (SBs) in science have been known for few decades; however, it seems that only recently have they become popular. An SB is a publication that "sleeps" for a long time and then almost suddenly awakes and becomes highly cited. SBs present interesting findings in science. Pediatrics research literature has not yet been analyzed for their presence, and 5 pediatrics SBs were discovered in this research. Their prevalence was approximately 0.011%. Some environments or periods are more "SB fertile" than others: 3 of 5 SBs were published in the journal Pediatrics, 4 originated from the United States, and 4 were published in the period from 1992 to 1993...
October 2016: Journal of the Medical Library Association: JMLA
https://www.readbyqxmd.com/read/27819347/engineering-of-escherichia-coli-for-direct-and-modulated-biosynthesis-of-poly-3-hydroxybutyrate-co-3-hydroxyvalerate-copolymer-using-unrelated-carbon-sources
#8
Kajan Srirangan, Xuejia Liu, Tam T Tran, Trevor C Charles, Murray Moo-Young, C Perry Chou
While poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] is a biodegradable commodity plastic with broad applications, its microbial synthesis is hindered by high production costs primarily associated with the supplementation of related carbon substrates (e.g. propionate or valerate). Here we report construction of engineered Escherichia coli strains for direct synthesis of P(3HB-co-3HV) from an unrelated carbon source (e.g. glucose or glycerol). First, an E. coli strain with an activated sleeping beauty mutase (Sbm) operon was used to generate propionyl-CoA as a precursor...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27801667/transposon-mediated-generation-of-bcr-abl1-expressing-transgenic-cell-lines-for-unbiased-sensitivity-testing-of-tyrosine-kinase-inhibitors
#9
Konstantin Byrgazov, Chantal Blanche Lucini, Bettina Berkowitsch, Margit Koenig, Oskar A Haas, Gregor Hoermann, Peter Valent, Thomas Lion
Point mutations in the ABL1 kinase domain are an important mechanism of resistance to tyrosine kinase inhibitors (TKI) in BCR-ABL1-positive and, as recently shown, BCR-ABL1-like leukemias. The cell line Ba/F3 lentivirally transduced with mutant BCR-ABL1 constructs is widely used for in vitro sensitivity testing and response prediction to tyrosine kinase inhibitors. The transposon-based Sleeping Beauty system presented offers several advantages over lentiviral transduction including the absence of biosafety issues, faster generation of transgenic cell lines, and greater efficacy in introducing large gene constructs...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27790711/transposon-mutagenesis-identifies-candidate-genes-that-cooperate-with-loss-of-transforming-growth-factor-beta-signaling-in-mouse-intestinal-neoplasms
#10
Shelli M Morris, Jerry Davison, Kelly T Carter, Rachele M O'Leary, Patty Trobridge, Sue E Knoblaugh, Lois L Myeroff, Sanford D Markowitz, Benjamin T Brett, Todd E Scheetz, Adam J Dupuy, Timothy K Starr, William M Grady
Colorectal cancer (CRC) results from the accumulation of gene mutations and epigenetic alterations in colon epithelial cells, which promotes CRC formation through deregulating signaling pathways. One of the most commonly deregulated signaling pathways in CRC is the transforming growth factor β (TGF-β) pathway. Importantly, the effects of TGF-β signaling inactivation in CRC are modified by concurrent mutations in the tumor cell, and these concurrent mutations determine the ultimate biological effects of impaired TGF-β signaling in the tumor...
October 28, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27732734/spinning-a-yarn-sleeping-beauty-and-anthrax
#11
Jason Giacomel, Iris Zalaudek
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27729044/retroviral-vectors-and-transposons-for-stable-gene-therapy-advances-current-challenges-and-perspectives
#12
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/27696897/sleeping-beauty-transposition-from-biology-to-applications
#13
Suneel A Narayanavari, Shreevathsa S Chilkunda, Zoltán Ivics, Zsuzsanna Izsvák
Sleeping Beauty (SB) is the first synthetic DNA transposon that was shown to be active in a wide variety of species. Here, we review studies from the last two decades addressing both basic biology and applications of this transposon. We discuss how host-transposon interaction modulates transposition at different steps of the transposition reaction. We also discuss how the transposon was translated for gene delivery and gene discovery purposes. We critically review the system in clinical, pre-clinical and non-clinical settings as a non-viral gene delivery tool in comparison with viral technologies...
October 4, 2016: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27694838/a-vector-platform-for-the-rapid-and-efficient-engineering-of-stable-complex-transgenes
#14
Carsten Jäckel, Melanie Schmitt Nogueira, Nadja Ehni, Christiane Kraus, Julius Ranke, Maike Dohmann, Elfriede Noessner, Peter J Nelson
We describe the generation of a set of plasmid vector tools that allow the rapid generation of complex-interacting stable transgenes in immortalized and primary cells. Of particular importance is inclusion of a mechanism to monitor the activation status of regulatory pathways via a reporter cassette (using Gaussia Luciferase), with control of additional transgene expression through doxycycline de-repression. The resulting vectors can be used to assess regulatory pathway activation and are well suited for regulatory pathway crosstalk studies...
October 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27650165/b-raf-mutation-in-non-small-cell-lung-cancer-the-sleeping-beauty-is-waking-up
#15
EDITORIAL
Christian Rolfo, Rafael Caparica
No abstract text is available yet for this article.
August 2016: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/27578760/sleeping-beauty-and-the-story-of-the-bacille-calmette-gu%C3%A3-rin-vaccine
#16
Helen A Fletcher
Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved vaccine safety but little change in efficacy in animal models. A second-generation recombinant BCG vaccine with an additional deletion of the nuoG gene (BCG ΔureC::hly ΔnuoG) shows improved efficacy in a mouse model compared to that of VPM1002...
2016: MBio
https://www.readbyqxmd.com/read/27574698/transcriptionally-regulated-and-nontoxic-delivery-of-the-hyperactive-sleeping-beauty-transposase
#17
Fabienne Cocchiarella, Maria Carmela Latella, Valentina Basile, Francesca Miselli, Melanie Galla, Carol Imbriano, Alessandra Recchia
The Sleeping Beauty (SB) transposase and, in particular, its hyperactive variant SB100X raises increasing interest for gene therapy application, including genome modification and, more recently, induced pluripotent stem cells (iPS) reprogramming. The documented cytotoxicity of the transposase, when constitutively expressed by an integrating retroviral vector (iRV), has been circumvented by the transient delivery of SB100X using retroviral mRNA transfer. In this study, we developed an alternative, safe, and efficient transposase delivery system based on a tetracycline-ON regulated expression cassette and the rtTA2(S)-M2 transactivator gene transiently delivered by integration-defective lentiviral vectors (IDLVs)...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27548616/redirecting-specificity-of-t-cells-using-the-sleeping-beauty-system-to-express-chimeric-antigen-receptors-by-mix-and-matching-of-vl-and-vh-domains-targeting-cd123-tumors
#18
Radhika Thokala, Simon Olivares, Tiejuan Mi, Sourindra Maiti, Drew Deniger, Helen Huls, Hiroki Torikai, Harjeet Singh, Richard E Champlin, Tamara Laskowski, George McNamara, Laurence J N Cooper
Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains...
2016: PloS One
https://www.readbyqxmd.com/read/27542769/survival-and-proliferation-of-neural-progenitor-derived-glioblastomas-under-hypoxic-stress-is-controlled-by-a-cxcl12-cxcr4-autocrine-positive-feedback-mechanism
#19
Alexandra A Calinescu, Viveka Nand Yadav, Erica Carballo, Padma Kadiyala, Dustin Tran, Daniel Zamler, Robert Doherty, Maithreyi Srikanth, Pedro R Lowenstein, Maria G Castro
PURPOSE: One likely cause of treatment failure in glioblastoma is the persistence of glioma stem-like cells (GSLCs), highly resistant to therapies currently employed. We found that CXCL12 has highest expression in glioma cells derived from neural progenitor cells (NPCs). The development and molecular signature of NPC-derived GBMs were analyzed and the therapeutic effect of blocking CXCL12 was tested. EXPERIMENTAL DESIGN: Tumors were induced by injecting DNA into the lateral ventricle of neonatal mice, using the Sleeping Beauty transposase method...
August 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27491640/enhanced-car-t-cell-engineering-using-non-viral-sleeping-beauty-transposition-from-minicircle-vectors
#20
R Monjezi, C Miskey, T Gogishvili, M Schleef, M Schmeer, H Einsele, Z Ivics, M Hudecek
Immunotherapy with T cell modified with gamma-retroviral or lentiviral (LV) vectors to express a chimeric antigen receptor (CAR) has shown remarkable efficacy in clinical trials. However, the potential for insertional mutagenesis and genotoxicity of viral vectors is a safety concern, and their cost and regulatory demands a roadblock for rapid and broad clinical translation. Here, we demonstrate that CAR T cells can be engineered through non-viral Sleeping Beauty (SB) transposition of CAR genes from minimalistic DNA vectors called minicircles (MCs)...
August 5, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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