A5081257024- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Hepatitis B Virus Studies
- Innovation and Socioeconomic Development
- Hepatitis C virus research
- Liver physiology and pathology
- Linguistic research and analysis
- Plant Virus Research Studies
- Virus-based gene therapy research
- Toxin Mechanisms and Immunotoxins
- CAR-T cell therapy research
- Animal Genetics and Reproduction
- Service and Product Innovation
- Transgenic Plants and Applications
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Linguistic Education and Pedagogy
- Click Chemistry and Applications
- Quantum-Dot Cellular Automata
- Cervical Cancer and HPV Research
- Viral Infections and Outbreaks Research
- Pharmacogenetics and Drug Metabolism
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
Utrecht University
2018-2024
Roche (Switzerland)
2014-2018
ConspectusThe discovery of CRISPR/Cas has revolutionized the field genome editing. CRIPSR/Cas components are part bacterial immune system and able to induce double-strand DNA breaks in genome, which resolved by endogenous repair mechanisms. The most relevant these error-prone nonhomologous end joining homology directed pathways. former can lead gene knockout introduction insertions deletions at cut site, while latter be used for correction based on a provided template. In this Account, we...
The discovery that the bacterial defense mechanism, CRISPR-Cas9, can be reprogrammed as a gene editing tool has revolutionized field of editing. CRISPR-Cas9 introduce double-strand break at specific targeted site within genome. Subsequent intracellular repair mechanisms double strand either lead to knock-out (via non-homologous end-joining pathway) or correction in presence DNA template via homology-directed repair. With latter, pathological mutations cut out and repaired. Advances are being...
Highlights•RG7834 is a novel orally bioavailable HBV viral gene expression inhibitor.•The effect of RG7834 on levels highly virus-specific.•The unique antiviral profile differentiated from that nucleos(t)ide analogues.•Combination with entecavir and/or PegIFNα improves the and potency.Graphical abstractAbstractBackground & AimsThe hallmarks chronic infection are high load (HBV DNA) even higher (>100-fold in excess virions) non-infectious membranous particles containing tolerogenic S antigen...
Early prediction of human clearance is often challenging, in particular for the growing number low-clearance compounds. Long-term vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved predictions. Here, cell line HepG2, iPSC-derived hepatocytes (iCell®), stem HepaRG™, hepatocyte co-cultures (HμREL™ HepatoPac®) were compared to primary suspension cultures with respect their key metabolic activities. Similar activities found long-term HμREL™,...
Natural killer (NK) cells participate in the immune system by eliminating cancer and virally infected through germline-encoded surface receptors. Their independence from prior activation as well their significantly lower toxicity have placed them spotlight an alternative to T for adoptive cell therapy (ACT). Engineering NK with mRNA has shown great potential ACT enhancing tumor targeting cytotoxicity. However, transfection of is challenging, most common delivery methods, such...
Chronic hepatitis B infection (CHB) is an area of high unmet medical need. Current standard-of-care therapies only rarely lead to a functional cure, defined as durable surface antigen (HBsAg) loss following treatment. The goal for next generation CHB achieve higher rate cure with finite treatment duration. To address this urgent need, we are developing liver-targeted single-stranded oligonucleotide (SSO) therapeutics based on the locked nucleic acid (LNA) platform. These LNA-SSOs target...
The genus beta human papillomaviruses (beta HPVs) cause cutaneous lesions and are thought to be involved in the initiation of some nonmelanoma skin cancers (NMSCs), particularly patients with genetic disorder epidermodysplasia verruciformis (EV). We have previously reported that at least two HPV E6 proteins bind and/or increase steady-state levels p53 squamous epithelial cells. This is contrast a well-characterized ability cancer-associated HPVs alpha HPV, which inactivate by targeting its...
Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European and belongs to RIP class II. The aim of this project was systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing apoptosis activation. For purpose, state the art imaging equipment automated image analysis algorithms were used. displayed very fast binding sugar...
The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse genetic disorders. However, for gene therapy applications, efficient delivery vehicle required, capable of delivering components into cytosol intended target cell population. In this study, we optimized formulation conditions lipid nanoparticles (LNP) ready-made ribonucleic protein (RNP). buffer composition during complexation and relative DOTAP concentrations were varied LNP encapsulating in-house...
The secondary structures of human hY1 and hY5 RNAs were determined using both chemical modification techniques enzymatic structure probing. results indicate that for RNA the largely corresponds to predicted by sequence alignment computerized energy-minimization. However, some important deviations observed. In case RNA, two regions forming a helix appeared be single-stranded. Furthermore, pyrimidine-rich region very resistant reagents under native conditions, although it was accessible...
Polymeric micelles (PMs) are promising platforms for enhanced tissue targeting of entrapped therapeutic agents. Strategies to circumvent premature release drugs include cross-linking the micellar core as well covalent attachment drug cargo. The chemistry employed obtain cross-linked needs be mild also allow entrapment fragile molecules, such certain peptides, proteins, oligonucleotides, and fluorescent dyes. Native chemical ligation (NCL) is a bio-orthogonal reaction between N-terminal...
The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse ge-netic disorders. However, for gene therapy applications efficient delivery vehicle required, capable of delivering components into cytosol intended target cell population. Once there, ribonucleoprotein complex (RNP) can be transported nucleus. Lipid nanoparticles (LNP) serve as promising candidates RNP. These vehicles have been optimized nucleic acids, such mRNA. Co-delivery Cas9 encoding mRNA...
The discovery that the bacterial defense mechanism, CRISPR-Cas9, can be reprogrammed as a gene editing tool has revolutionized field of editing. CRISPR-Cas9 introduce double-strand break at specific targeted site within genome. Subsequent intracellular repair mechanisms double strand either lead to knock-out (via non-homologous end-joining pathway) or correction in presence DNA template via homology-directed repair. With latter, pathological mutations cut out and repaired. Advances are being...
Abstract CRISPR gene therapy holds the potential to cure a variety of genetic diseases by targeting causative mutations and introducing double stranded DNA breaks, subsequently allowing host repair mechanisms introduce mutations. One option precise corrections is via homology-directed (HDR) pathway. HDR can range desired dictated template which corrected sequence written into targeted gene. The problem in utilizing this pathway that CRISPR-induced breaks are repaired more often through...