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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
#1
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/28122714/sleeping-beauty-awakening-urothelium-from-its-slumber
#2
Zarine R Balsara, Xue Li
The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens, or excessive, thereby setting the stage for tumor development...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28115300/research-progress-of-tc1-mariner-superfamily
#3
Shen Dan, Chen Cai, Wang Saisai, Chen Wei, Gao Bo, Song Chengyi
With the rapid improvement of sequencing techniques, more and more genome annotations reveal the transposons are the important components of most genomes and present on almost all organisms. Among them, the Tc1/Mariner superfamily represents the most widespread DNA transposons. Until now, fourteen active Tc1/Mariner transposons (Minos, Mos1, etc.) have been identified and some highly active artificial transposons have been created through molecular reconstruction, such as Sleeping Beauty (SB). The transposons such as SB and Mos1 have been widely used as gene transfer vectors in the fields of transgenosis, gene trapping and gene therapy...
January 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28081459/targeted-delivery-of-in-situ-pcr-amplified-sleeping-beauty-transposon-genes-to-cancer-cells-with-lipid-based-nanoparticle-like-protocells
#4
Kun Ma, Duo Fu, Dongli Yu, Changhao Cui, Li Wang, Zhaoming Guo, Chuanbin Mao
A Sleeping Beauty (SB) transposon system is made of a transposon plasmid (containing gene encoding a desired functional or therapeutic protein) and a transposase plasmid (encoding an enzyme capable of cutting and pasting the gene into the host cell genome). It is a kind of natural, nonviral gene delivery vehicle, which can achieve efficient genomic insertion, providing long-term transgenic expression. However, before the SB transposon system could play a role in promoting gene expression, it has to be delivered efficiently first across cell membrane and then into cell nuclei...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#5
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28035654/seven-days-post-injury-fate-and-effects-of-genetically-labelled-adipose-derived-mesenchymal-cells-on-a-rat-traumatic-brain-injury-experimental-model
#6
Ioanna Dori, Spyros Petrakis, Aggeliki Giannakopoulou, Chryssa Bekiari, Ioannis Grivas, Evangelia K Siska, Georgios Koliakos, Georgios C Papadopoulos
Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissue-derived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus...
December 30, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/28027893/correction-of-recessive-dystrophic-epidermolysis-bullosa-by-transposon-mediated-integration-of-col7a1-in-transplantable-patient-derived-primary-keratinocytes
#7
Maria Carmela Latella, Fabienne Cocchiarella, Laura De Rosa, Giandomenico Turchiano, Manuel A F V Gonçalves, Fernando Larcher, Michele De Luca, Alessandra Recchia
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects in type-VII collagen (C7), a protein encoded by the COL7A1 gene and essential for anchoring fibril formation at the dermal-epidermal junction. Gene therapy of RDEB is based on transplantation of autologous epidermal grafts generated from gene-corrected keratinocytes sustaining C7 deposition at the dermal-epidermal junction. Transfer of the COL7A1 gene is complicated by its very large size and repetitive sequence. We report a gene delivery approach based on the Sleeping beauty transposon, which allows integration of a full-length COL7A1 cDNA and secretion of C7 at physiological levels in RDEB keratinocytes without rearrangements or detrimental effects on their clonogenic potential...
December 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-co-expression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#8
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27966608/slit-robo-gtpase-activating-protein-2-as-a-metastasis-suppressor-in-osteosarcoma
#9
Tracy A Marko, Ghaidan A Shamsan, Elizabeth N Edwards, Paige E Hazelton, Susan K Rathe, Ingrid Cornax, Paula R Overn, Jyotika Varshney, Brandon J Diessner, Branden S Moriarity, M Gerard O'Sullivan, David J Odde, David A Largaespada
Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913727/regulated-complex-assembly-safeguards-the-fidelity-of-sleeping-beauty-transposition
#10
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...
January 9, 2017: 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
February 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27732734/spinning-a-yarn-sleeping-beauty-and-anthrax
#20
Jason Giacomel, Iris Zalaudek
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
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