Genomes and Genes
Affiliation: Katholieke Universiteit Leuven
- Transient Expression of an LEDGF/p75 Chimera Retargets Lentivector Integration and Functionally Rescues in a Model for X-CGDSofie Vets
Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Molecular Virology and Gene Therapy, KU Leuven, Leuven, Belgium
Mol Ther Nucleic Acids 2:e77. 2013..Molecular Therapy - Nucleic Acids (2013) 2, e77; doi:10.1038/mtna.2013.4; published online 5 March 2013...
- LEDGF/p75-independent HIV-1 replication demonstrates a role for HRP-2 and remains sensitive to inhibition by LEDGINsRik Schrijvers
Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
PLoS Pathog 8:e1002558. 2012..These results further support the potential of LEDGINs as allosteric integrase inhibitors...
- High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE regionJan De Rijck
Laboratory for Molecular Virology and Gene Therapy, KULeuven and IRC KULAK, Kapucijnenvoer 33, B 3000 Leuven, Belgium
Nucleic Acids Res 38:6135-47. 2010..Interestingly, some associations did not correlate with HIV-1 integration indicating that not all LEDGF/p75 complexes on the chromosome are amenable to HIV-1 integration...
- Role of the PWWP domain of lens epithelium-derived growth factor (LEDGF)/p75 cofactor in lentiviral integration targetingRik Gijsbers
Division of Molecular Medicine, KU Leuven, 3000 Leuven, Belgium
J Biol Chem 286:41812-25. 2011....
- Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIVAnneleen Hombrouck
The Laboratory for Molecular Virology and Gene Therapy, KULeuven and IRC KULAK, Leuven, Flanders, Belgium
PLoS Pathog 3:e47. 2007..Moreover, the role of LEDGF/p75 in targeting integration will stimulate research on strategies to direct gene therapy vectors into safe landing sites...
- Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZKoen Bartholomeeusen
Laboratory for Molecular Virology and Gene Therapy, Division of Molecular Medicine, Katholieke Universiteit Leuven, Kapucijnenvoer 33, Flanders, Belgium
J Biol Chem 284:11467-77. 2009..The finding that LEDGF/p75 is capable of interacting with a DDE domain protein that is not a lentiviral integrase points to a profound role of LEDGF/p75 in DDE domain protein function...
- A p-[18F]fluoroethoxyphenyl bicyclic nucleoside analogue as a potential positron emission tomography imaging agent for varicella-zoster virus thymidine kinase gene expressionSatish K Chitneni
Molecular Small Animal Imaging Center, Laboratory for Radiopharmacy Faculty of Pharmaceutical Sciences, Department of Nuclear Medicine, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium
J Med Chem 50:6627-37. 2007..LC-MS analysis confirmed the formation of monophosphate derivative of 5 upon catalysis by VZV TK. In vivo studies of this new reporter gene/probe system are in progress...
- The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tetheringJelle Hendrix
Laboratory for Biomolecular Dynamics, University of Leuven, Leuven, Flanders, B 3000, Belgium
Nucleic Acids Res 39:1310-25. 2011..The PWWP is crucial for locking the complex on chromatin. We propose a scan-and-lock model for LEDGF/p75, unifying paradoxical notions of transcriptional co-activation and lentiviral integration targeting...
- Lens epithelium-derived growth factor/p75 qualifies as a target for HIV gene therapy in the NSG mouse modelSofie Vets
Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
Mol Ther 20:908-17. 2012..LEDGF(325-530) overexpression potently inhibits HIV replication in vivo and protects against HIV mediated cell killing of primary CD(4)(+) T-cells...
- Synthesis and biological evaluation of (11)C-labeled beta-galactosyl triazoles as potential PET tracers for in vivo LacZ reporter gene imagingSofie Celen
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Herestraat 49 bus 821, BE 3000 Leuven, Belgium
Bioorg Med Chem 17:5117-25. 2009..In vitro evaluation in HEK-293T cells showed an increased cell uptake for the more lipophilic [(11)C]-13, however, there was no statistically higher uptake in LacZ expressing cells compared to control cells...
- Immunohistochemical detection of transgene expression in the brain using small epitope tagsEvy Lobbestael
Laboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
BMC Biotechnol 10:16. 2010..In order to minimize impact on the bioactivity and biodistribution of the overexpressed protein, preference is given to small tags...
- LEDGF hybrids efficiently retarget lentiviral integration into heterochromatinRik Gijsbers
Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
Mol Ther 18:552-60. 2010..Thus, engineered LEDGF/p75 chimeras provide technology for controlling integration site selection by lentiviral vectors...
- Preliminary validation of varicella zoster virus thymidine kinase as a novel reporter gene for PETChristophe M Deroose
Division of Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
Nucl Med Biol 39:1266-74. 2012..We investigated varicella zoster virus thymidine kinase (VZV-tk) as new PRG with radiolabeled bicyclic nucleoside analogues (BCNAs) as PET tracers...
- Highly efficient multicistronic lentiviral vectors with peptide 2A sequencesAbdelilah Ibrahimi
Molecular Medicine, Katholieke Universiteit Leuven, B 3000 Leuven, Flanders, Belgium
Hum Gene Ther 20:845-60. 2009..Last, using various peptide 2A sequences, we engineered the triple reporter LV-3R (i.e., eGFP, fLuc, HSV1-sr39tk), enabling efficient multimodality readouts in vivo...
- Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75Koen Bartholomeeusen
Molecular Medicine, KULeuven and IRC KULAK, Leuven, Belgium
J Mol Biol 372:407-21. 2007..Furthermore, JPO2 over-expression activated transcription from the HIV-1 LTR...
- Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virusLinos Vandekerckhove
Molecular Medicine, K U Leuven and IRC KULAK, Kapucijnenvoer 33, B 3000 Leuven, Flanders, Belgium
J Virol 80:1886-96. 2006..Altogether, our data validate LEDGF/p75 as an important cellular cofactor for HIV integration and as a potential target for antiviral drug development...
- Characterization of rare lens epithelium-derived growth factor/p75 genetic variants identified in HIV-1 long-term nonprogressorsRik Schrijvers
Molecular Virology and Gene Therapy, KU Leuven, Leuven, Flanders, Belgium
AIDS 27:539-43. 2013..Here, we study two LEDGF/p75 exonic variants I436S and T473I, identified in HIV-1 long-term nonprogressors, together with Q472L...
- Overexpression of the lens epithelium-derived growth factor/p75 integrase binding domain inhibits human immunodeficiency virus replicationJan De Rijck
Molecular Medicine, KU Leuven and IRC KULAK, Kapucijnenvoer 33 VCTB 5, B 3000 Leuven, Belgium
J Virol 80:11498-509. 2006..These data support LEDGF/p75 as an important cofactor for HIV replication and provide proof of concept for the LEDGF/p75-integrase interaction as a novel target for treating HIV-1 infection...
- Synthesis and biological evaluation of an 123I-labeled bicyclic nucleoside analogue (BCNA) as potential SPECT tracer for VZV-tk reporter gene imagingSatish K Chitneni
Laboratory for Radiopharmacy, Katholieke Universiteit Leuven, Leuven, Belgium
Bioorg Med Chem Lett 17:3458-62. 2007..2 microM). Biodistribution of [(123)I]-4 was examined in normal mice. Evaluation of [(123)I]-4 in HEK-293T cells showed 1.74-fold higher accumulation in VZV-TK-expressing cells compared to control cells...
- Phage display-directed discovery of LEDGF/p75 binding cyclic peptide inhibitors of HIV replicationBelete A Desimmie
Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, K U Leuven and IRC KULAK, Flanders, Belgium
Mol Ther 20:2064-75. 2012..Our work provides proof-of-concept for direct targeting of LEDGF/p75 as novel therapeutic strategy and the CPs thereby serve as scaffold for future development of new HIV therapeutics...
- Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2Anisoara Cimpean
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B 3000 Leuven, Belgium
Biochem J 381:71-7. 2004..Our data suggest that the distinct activities of NPP1 and NPP2 stem from multiple differences throughout the polypeptide chain...
- Comparison of lentiviral vector titration methodsMartine Geraerts
Laboratory for Molecular Virology and Gene Therapy, K U Leuven and IRC KULAK, Flanders, Belgium
BMC Biotechnol 6:34. 2006..Methods are required to analyze the quality of lentiviral vector production, the efficiency of gene transfer and the extent of therapeutic gene expression...
- Noninvasive and quantitative monitoring of adult neuronal stem cell migration in mouse brain using bioluminescence imagingVeerle Reumers
Neurobiology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
Stem Cells 26:2382-90. 2008..Long-term expression of brain-derived neurotrophic factor in the subventricular zone attenuated neurogenesis, as detected by histology and BLI. In vivo monitoring of the impact of drugs or genes on adult neurogenesis is now within reach...
- LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virionsBelete Ayele Desimmie
Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Molecular Virology and Gene Therapy, KU Leuven, Leuven, Flanders, Belgium
Retrovirology 10:57. 2013..They block HIV-1 integration by abrogating the interaction between LEDGF/p75 and IN as well as by allosterically inhibiting the catalytic activity of IN...
- HRP-2 determines HIV-1 integration site selection in LEDGF/p75 depleted cellsRik Schrijvers
Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Flanders, Belgium
Retrovirology 9:84. 2012..We previously identified Hepatoma-derived growth factor related protein 2 (HRP-2) as a factor mediating LEDGF/p75-independent HIV-1 replication. However, the role of HRP-2 in HIV-1 integration site selection was not addressed...
- Transportin-SR2 imports HIV into the nucleusFrauke Christ
Laboratory for Molecular Virology and Gene Therapy, KU Leuven and IRC, Kapucijnenvoer 33, B 3000 Leuven, Flanders, Belgium
Curr Biol 18:1192-202. 2008..This requires import of the preintegration complex (PIC) through the nuclear pore. Although many cellular and viral determinants have been proposed, the mechanism leading to nuclear import is not yet understood...
- Synthesis and evaluation of 18F- and 11C-labeled phenyl-galactopyranosides as potential probes for in vivo visualization of LacZ gene expression using positron emission tomographySofie Celen
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium
Bioconjug Chem 19:441-9. 2008..Further structural modifications to improve the diffusion over the tumor cell membrane and to increase retention in beta-gal expressing cells may lead to more favorable in vivo imaging probes...
- A PET brain reporter gene system based on type 2 cannabinoid receptorsCaroline Vandeputte
Division of Nuclear Medicine, University Hospital and K U Leuven, Leuven, Belgium
J Nucl Med 52:1102-9. 2011..Here we report the first, to our knowledge, PET reporter system for imaging gene expression in the intact brain...
- Interplay between HIV entry and transportin-SR2 dependencyWannes Thys
Laboratory of Molecular Virology and Gene Therapy, Katholieke Universiteit Leuven, Kapucijnenvoer 33, VCTB 5, B 3000 Leuven, Flanders, Belgium
Retrovirology 8:7. 2011....
- PEAR1 attenuates megakaryopoiesis via control of the PI3K/PTEN pathwayAlexandre Kauskot
Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
Blood 121:5208-17. 2013..In summary, this is the first demonstration that PEAR1 influences the PI3K/PTEN pathway, a critical determinant of Akt phosphorylation, itself controlling megakaryopoiesis and thrombopoiesis. ..
- Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic miceMattia Quattrocelli
Translational Cardiomyology Lab, Stem Cell Biology and Embryology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
J Am Heart Assoc 2:e000284. 2013..However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown...
- Efficient gene transfer into the mouse lung by fetal intratracheal injection of rAAV2/6.2Marianne Carlon
Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Flanders, Belgium
Mol Ther 18:2130-8. 2010....
- The BET family of proteins targets moloney murine leukemia virus integration near transcription start sitesJan De Rijck
Laboratory for Molecular Virology and Gene Therapy, KU Leuven, 3000 Leuven, Belgium
Cell Rep 5:886-94. 2013..Together, these data validate BET proteins as MLV integration targeting factors...
- The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic siteRik Gijsbers
Afdeling Biochemie, Faculteit Geneeskunde, University of Leuven, Herestraat 49, B 3000 Leuven, Belgium
FEBS Lett 538:60-4. 2003..In comparing the substrate specificity of NPP2 and the closely related NPP1 and NPP3, we found that only NPP2 displayed a lysophospholipase D activity, whereas NPP1 and NPP3 had a much higher nucleotide pyrophosphatase activity...
- Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's diseaseLinda Vercammen
Laboratory for Neurobiology and Gene Therapy, Molecular Medicine, K U Leuven, Kapucijnenvoer 33 VCTB 5, B 3000 Leuven, Flanders, Belgium
Mol Ther 14:716-23. 2006..These data support the therapeutic potential of parkin for the treatment of not only familial but also sporadic Parkinson's disease...
- Immunological ignorance allows long-term gene expression after perinatal recombinant adeno-associated virus-mediated gene transfer to murine airwaysMarianne S Carlon
1 Laboratory of Molecular Virology and Gene Therapy, Katholieke Universiteit KU Leuven, Leuven, Belgium
Hum Gene Ther 25:517-28. 2014..Together, these data provide a basis to further explore perinatal gene therapy for pulmonary conditions with adequate gene expression up to 7 months. ..
- Viral vectors expressing a single microRNA-based short-hairpin RNA result in potent gene silencing in vitro and in vivoLuísa Osório
KU Leuven, Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven, Belgium
J Biotechnol 169:71-81. 2014....
- Upscaling of lentiviral vector production by tangential flow filtrationMartine Geraerts
Laboratory for Molecular Virology and Gene Therapy, K U Leuven, Belgium
J Gene Med 7:1299-310. 2005..Application of these vectors for gene therapy or for the creation of animal models for neurodegenerative diseases requires standardization and upscaling of lentiviral vector production methods...
- Optimization of multimodal imaging of mesenchymal stem cells using the human sodium iodide symporter for PET and Cerenkov luminescence imagingEsther Wolfs
Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
PLoS ONE 9:e94833. 2014....
- Synthesis and preliminary evaluation of 18F- or 11C-labeled bicyclic nucleoside analogues as potential probes for imaging varicella-zoster virus thymidine kinase gene expression using positron emission tomographySatish K Chitneni
Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, K U Leuven, Leuven, Belgium
J Med Chem 50:1041-9. 2007..These data warrant further evaluation of these tracers as noninvasive imaging agents for VZV infection and VZV-tk reporter gene expression in vivo...
- Functional characterization of the non-catalytic ectodomains of the nucleotide pyrophosphatase/phosphodiesterase NPP1Rik Gijsbers
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Campus Gasthuisberg, Herestraat 49, B 3000 Leuven, Belgium
Biochem J 371:321-30. 2003..Our data suggest that the non-catalytic ectodomains contribute to the subunit structure, stability and function of NPP1-3...
- 1,25-Dihydroxyvitamin D3 and the aging-related forkhead box O and sestrin proteins in osteoblastsGuy Eelen
Laboratory for Clinical and Experimental Endocrinology, KU Leuven, B 3000 Leuven, Belgium
J Steroid Biochem Mol Biol 136:112-9. 2013..This article is part of a Special Issue entitled 'Vitamin D Workshop'...
- Recipient leukocyte infusion enhances the local and systemic graft-versus-neuroblastoma effect of allogeneic bone marrow transplantation in miceLeen Willems
Laboratory of Experimental Transplantation, KU Leuven, Herestraat 49, Box 811, 3000, Leuven, Belgium
Cancer Immunol Immunother 62:1733-44. 2013..Our data indicate that RLI may provide combined T-cell and NK-cell reactivity effectively targeting Neuro2A neuroblastoma...
- Regulator of G-protein signaling 18 controls megakaryopoiesis and the cilia-mediated vertebrate mechanosensory systemSophie Louwette
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O and N1, Herestraat 49, Box 911, 3000 Leuven, Belgium
FASEB J 26:2125-36. 2012..In summary, our study is the first to show that RGS18 regulates megakaryopoiesis but also reveals its unexpected role in ciliogenesis, at least in lower vertebrates, via interference with Wnt signaling...
- miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitorsStefania Crippa
Translational Cardiomyology Laboratory, Interdepartmental Stem Cell Institute, Catholic University of Leuven, 3000 Leuven, Belgium
J Cell Biol 193:1197-212. 2011....