A5012452525- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Hemophilia Treatment and Research
- Viral Infectious Diseases and Gene Expression in Insects
- Muscle Physiology and Disorders
- Pluripotent Stem Cells Research
- Viral Infections and Immunology Research
- Tissue Engineering and Regenerative Medicine
- Platelet Disorders and Treatments
- Animal Genetics and Reproduction
- Viral gastroenteritis research and epidemiology
- Biomedical Ethics and Regulation
- Genetic Neurodegenerative Diseases
- Immune Cell Function and Interaction
- Liver physiology and pathology
- Mesenchymal stem cell research
- Blood Coagulation and Thrombosis Mechanisms
- Electrospun Nanofibers in Biomedical Applications
- Neurogenetic and Muscular Disorders Research
- Cytomegalovirus and herpesvirus research
- Mitochondrial Function and Pathology
- T-cell and B-cell Immunology
- Biochemical and Molecular Research
KU Leuven
2015-2024
Vrije Universiteit Brussel
2010-2024
SingHealth
2024
Bio-Medical Science (South Korea)
2003-2019
Universidad Autónoma de Madrid
2016
VIB-KU Leuven Center for Cancer Biology
2016
Inserm
2012-2015
Centre National de la Recherche Scientifique
2012-2015
Centre de Recherche en Myologie
2015
Institut de Myologie
2015
Abstract Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and countless transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline enables direct side-by-side comparison of pre-selected AAV capsids in high-throughput same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, create three independent libraries...
Transposon-based gene vectors have become indispensable tools in vertebrate genetics for applications ranging from insertional mutagenesis and transgenesis model species to therapy humans. The transposon toolkit is expanding, but a careful, side-by-side characterization of the diverse systems has been lacking. Here we compared Sleeping Beauty (SB), piggyBac (PB), Tol2 transposons with respect overall activity, overproduction inhibition (OPI), target site selection, transgene copy number as...
Abstract Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity stable expression and the lack preexisting immunity in most human subjects. However, use integrating may raise some concerns about potential risk insertional mutagenesis. Here we investigated liver transfer by integrase-defective lentiviral (IDLVs) containing an inactivating mutation integrase (D64V). Hepatocyte-targeted using IDLVs resulted sustained robust induction immune tolerance...
Gene therapy with lentiviral vectors targeting transgene expression to hepatocytes provides stable reconstitution of clotting activity in dogs hemophilia B and does not show genotoxicity tumor-prone mice.
CRISPR/Cas9 is an attractive platform to potentially correct dominant genetic diseases by gene editing with unprecedented precision. In the current proof-of-principle study, we explored use of for gene-editing in myotonic dystrophy type-1 (DM1), autosomal-dominant muscle disorder, excising CTG-repeat expansion 3′-untranslated-region (UTR) human protein kinase (DMPK) DM1 patient-specific induced pluripotent stem cells (DM1-iPSC), DM1-iPSC-derived myogenic and myoblasts. To eliminate...
Bioengineering of viral vectors for therapeutic gene delivery is a pivotal strategy to reduce doses, facilitate manufacturing, and improve efficacy patient safety. Here, we engineered myotropic adeno-associated (AAV) via semirational, combinatorial approach that merges AAV capsid peptide library screens. We first identified shuffled AAVs with increased specificity in the murine skeletal muscle, diaphragm, heart, concurrent liver detargeting. Next, boosted muscle by displaying on surface. In...
Hemophilia A is caused by a deficiency in coagulation factor VIII (FVIII) and predisposes to spontaneous bleeding that can be life-threatening or lead chronic disabilities. It well suited for gene therapy because moderate increase plasma FVIII concentration has therapeutic effects. Improved retroviral vectors expressing high levels of human were pseudotyped with the vesicular stomatitis virus G glycoprotein, concentrated high-titers (10 9 –10 10 colony-forming units/ml), injected...
Abstract Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at site infection. Although classically activated monocytic assumed be major source TNF NO during Trypanosoma brucei infection, their cellular origin remains unclear. In this study, we show bone marrow-derived accumulate TNF/inducible synthase-producing (TIP-DCs) in spleen, liver, lymph nodes T. brucei-infected mice. TIP-DCs have been shown play a beneficial...
Colon cancer accounts for more than 10% of all deaths annually. Our genetic evidence from Drosophila and previous in vitro studies mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function the group proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 human ATOH1 act as tumor suppressor genes vivo. Genetic knockouts molecular analyses cell lines support a ATOH1. antagonizes formation growth by regulating proliferation...
Background— The progressive shift from a young to an aged heart is characterized by alterations in the cardiac matrix. present study investigated whether matricellular protein thrombospondin-2 (TSP-2) may affect dimensions and function with physiological aging of heart. Methods Results— TSP-2 knockout (KO) wild-type mice were followed up age 60 weeks. Survival rate, function, morphology did not differ at KO compared mice. However, >55% died between 24 weeks age, whereas <10% died. In...
The robustness and safety of liver-directed gene therapy can be substantially improved by enhancing expression the therapeutic transgene in liver. To achieve this, we developed a new approach rational silico vector design. This relies on genome-wide bio-informatics strategy to identify cis-acting regulatory modules (CRMs) containing evolutionary conserved clusters transcription factor binding site motifs that determine high tissue-specific expression. Incorporation these CRMs into...