A5076460713- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- RNA regulation and disease
- Protein Degradation and Inhibitors
- interferon and immune responses
- Pluripotent Stem Cells Research
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Tracheal and airway disorders
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- CAR-T cell therapy research
- T-cell and Retrovirus Studies
- RNA Research and Splicing
- Retinal Development and Disorders
- Cutaneous lymphoproliferative disorders research
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- Airway Management and Intubation Techniques
- Plant Surface Properties and Treatments
- Hippo pathway signaling and YAP/TAZ
- Tumors and Oncological Cases
- NF-κB Signaling Pathways
- Viral Infections and Immunology Research
Aarhus University
2017-2024
Institute for Biomedicine
2020
Bispebjerg Hospital
1932-1965
Kommunedata (Denmark)
1964
Implementation of therapeutic in vivo gene editing using CRISPR/Cas relies on potent delivery tools. Administration ribonucleoprotein (RNP) complexes consisting Cas protein and single guide RNA (sgRNA) offers short-lived activity safety advantages over conventional viral non-viral approaches. By engineering lentivirus-derived nanoparticles (LVNPs) to facilitate RNP delivery, we demonstrate effective administration SpCas9 as well SpCas9-derived base prime editors (BE/PE) leading recipient...
Virus-based gene therapy by CRISPR/Cas9-mediated genome editing and knockout may provide a new option for treatment of inherited acquired ocular diseases the retina. In support this notion, we show that Streptococcus pyogenes (Sp) Cas9, delivered lentiviral vectors (LVs), can be used in vivo to selectively ablate vascular endothelial growth factor A (Vegfa) mice. By generating LVs encoding SpCas9 targeted Vegfa, parallel fluorescent eGFP marker protein, demonstrate robust Vegfa leads...
Abstract Prime editing (PE) is a novel CRISPR-derived genome technique facilitating precision without double-stranded DNA breaks. PE, mediated by Cas9-reverse transcriptase fusion protein, based on dual-functioning prime guide RNAs (pegRNAs), serving both as molecules and templates carrying the desired edits. Due to such diverse functions, manual pegRNA design subject error not suited for large-scale setups. Here, we present pegIT, user-friendly web tool rapid numerous user-defined edits,...
Abstract Introduction In epithelial cancers, truncated O-glycans, such as the Thomson-nouveau antigen (Tn) and its sialylated form (STn), are upregulated on cell surface associated with poor prognosis immunological escape. Recent studies have shown that these carbohydrate epitopes facilitate cancer development can be targeted therapeutically; however, mechanism underpinning their expression remains unclear. Methods To identify genes directly influencing of cancer-associated we conducted an...
The frontline therapy R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) has remained unchanged two decades despite numerous Phase III clinical trials investigating new alternatives. Multiple studies have uncovered genetic subtypes of DLBCL enabling a targeted approach. To further pave the way precision oncology, we perform genome-wide CRISPR screening to uncover cellular response one components R-CHOP, vincristine, in cell line SU-DHL-5. We discover important pathways and...
Abstract A major clinical challenge of diffuse large B-cell lymphoma (DLBCL) is that up to 40% patients have refractory disease or relapse after initial response therapy as a result drug-specific molecular resistance. The purpose the present study was investigate microRNA (miRNA) involvement in vincristine resistance DLBCL, which pursued by functional vitro analysis DLBCL cell lines and outcome with treated rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP)....
Diffuse large B‐cell lymphoma (DLBCL) is characterized by extensive genetic heterogeneity, and this results in unpredictable responses to the current treatment, R‐CHOP, which consists of a cancer drug combination supplemented with humanized CD20‐targeting monoclonal antibody rituximab. Despite improvements patient response rate through rituximab addition treatment plan, up 40% DLBCL patients end relapsed or refractory state due inherent acquired resistance regimen. Here, we employ lentiviral...
Prime editing is a novel genome technology that allows wide range of tailored genomic alterations. does not involve homologous recombination, but suffers from low efficacy. Here, we demonstrate piggyPrime, transfected single-vector system based on piggyBac DNA transposition for integration all prime components in human cells allowing easy and effective transgenesis with efficacies up to 100% cell lines.
Forty-five anesthetised guinea-pigs were subjected to white noise at a level of 127 db for one hour, as free field stimulus. At intervals from 0 up 31 days after the application stimulus, animals underwent autopsy and examined by cytophotometry degree cytoplasmic baso-philia in cells spiral ganglion, following staining gallocyanin-chrome alum pH 1.64, indicate relative changes RNA content. The ganglion also measured possible size. An initial fall basophilia was found, but course two weeks...
The innate immune system represents a balanced first line of defense against infection. Type I interferons (IFNs) are key regulators the response to viral infections with an essential early wave IFN-β expression, which is conditional, time-restricted, and stochastic in its nature. possibility precisely monitor individual cells active IFNB1 transcription during signaling requires robust reporter that mimics endogenous signal. Here, we present based on expression destabilized version eGFP...
Antibody-based immunotherapy targeting the interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 has shown impressive clinical outcomes in various cancer types, including nonsmall lung (NSCLC). However, regulatory mechanisms this immune checkpoint pathway still needs clarification. PD-L2 is structurally homologous to a second PD-1 ligand. Alternative mRNA splicing from CD274 PDCD1LG2 genes holds potential generate isoforms, respectively, with novel functionality regulation...
A prognostic 3-miRNA classifier for early-stage mycosis fungoides has been developed recently, with miR-106b providing the strongest power. The aim of this study was to investigate molecular function in disease progression. cellular localization skin biopsies determined by situ hybridization. regulatory role assessed transient inhibitor/mimic transfection 2 derived cell lines, followed quantitative real-time PCR (RT-qPCR), western blotting and a proliferation assay. MiR-106b found be...
Locus-directed DNA cleavage induced by the CRISPR-Cas9 system triggers repair mechanisms allowing gene or targeted insertion of foreign DNA. For to be successful, availability a homologous donor template needs timed with Cas9 endonuclease guided target-specific single guide RNA (sgRNA). We present novel approach for based on integrase-defective lentiviral vector (IDLV) carrying off switch. Gene using this benefits from transposon-based stable expression, which is switched excision-only...
Adeno-tonsillectomy is the most frequent surgical intervention of de head and neck in paediatrics industrialised countries one common operations Mayor Day Case Surgery; although not void risks which can be fatal. Complications or anaesthetics nature, serious complications being postoperative bleed. Among risk factors we highlight: age younger then three, female gender, duration surgery, incomplete haemostasis, coagulophaties. These could related to delayed oral intake. Postoperative bleed...
RésuméEn vue de l'étude des modifications fonctionnelles la cellule du ganglion Corti, cobayes furent exposés à un bruit blanc l'intensité 127 décibels. 9 subirent une excitation sonore pendant période d'une demiheure jusqu'à 6 heures et disséqués sitôt après. 42 excités heure ont survécu 1 31 jours avant dissection. Sur préparations obtenues par dissection fut exécuté, après coloration l'alun chrome gallo-cyanine a.m. Einarson, examen cytophotométrique basophilisme cytoplasmatique cellules...
Abstract The frontline therapy R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) has remained unchanged two decades despite numerous phase III clinical trials investigating new alternatives. Multiple studies have uncovered genetic subtypes of DLBCL enabling a targeted approach. To further pave the way precision oncology, we perform genome-wide CRISPR screening to uncover cellular response one components R-CHOP, vincristine, in cell line SU-DHL-5. We discover important pathways...
Abstract Background: Overtreatment of indolent prostate cancer (PC) and delayed treatment aggressive PC is common due to suboptimal risk stratification tools, thus warranting identification novel prognostic biomarkers. Although a few long non-coding RNAs (lncRNAs) with biomarker potential in are known, the majority lncRNAs remain uncharacterized. Here, we aimed identify lncRNA candidates. We hypothesized that strong candidates would have functional role driving progression addition their...