A5076054268- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Head and Neck Cancer Studies
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Respiratory and Cough-Related Research
- Radiomics and Machine Learning in Medical Imaging
- Advanced biosensing and bioanalysis techniques
- Cystic Fibrosis Research Advances
- Sinusitis and nasal conditions
- Medical Imaging Techniques and Applications
- Neonatal Respiratory Health Research
- Virus-based gene therapy research
- Lung Cancer Diagnosis and Treatment
- Energy Harvesting in Wireless Networks
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Inhalation and Respiratory Drug Delivery
- Cancer Diagnosis and Treatment
- Dendrimers and Hyperbranched Polymers
- Advanced Polymer Synthesis and Characterization
- Otitis Media and Relapsing Polychondritis
- Thyroid Cancer Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Nasal Surgery and Airway Studies
- Thyroid and Parathyroid Surgery
Nationwide Children's Hospital
2023-2025
The Ohio State University
2023-2024
St James's University Hospital
2014-2024
Leeds Teaching Hospitals NHS Trust
2013-2023
California Institute for Regenerative Medicine
2023
Stanford University
2018-2023
Southern Research Institute
2023
Duke University
2021
University College London
2021
National Cancer Centre Japan
2020
The Cas9/guide RNA (Cas9/gRNA) system is commonly used for genome editing. mRNA expressing Cas9 can induce innate immune responses, reducing expression. First-generation mRNAs were modified with pseudouridine and 5-methylcytosine to reduce responses. We combined four approaches produce more active, less immunogenic second-generation mRNAs. First, we developed a novel co-transcriptional capping method yielding natural Cap 1. Second, screened nucleotides in identify modifications that increase...
Background: Chronic rhinosinusitis (CRS) with nasal polyposis is common. The long-term efficacy and safety of approaches to medical management are not well-known. Objective: To evaluate the a 2-week regimen oral steroid therapy followed by 26 weeks sequential topical maintenance therapy. Design: Parallel randomized trial computer-generated block randomization central allocation. Patients investigators were blinded group assignment. (ClinicalTrials.gov registration number: NCT00788749)...
Genome-editing technologies are currently being translated to the clinic. However, cellular effects of editing machinery have yet be fully elucidated. Here, we performed global microarray-based gene expression measurements on human CD34+ hematopoietic stem and progenitor cells that underwent editing. We probed entire process as well each component individually, including electroporation, Cas9 (mRNA or protein) with chemically modified sgRNA, AAV6 transduction. identified differentially...
Engineered nuclease-mediated gene targeting through homologous recombination (HR) in hematopoietic stem and progenitor cells (HSPCs) has the potential to treat a variety of genetic hematologic immunologic disorders. Here, we identify critical parameters reproducibly achieve high frequencies RNA-guided (single-guide RNA [sgRNA]; CRISPR)-Cas9 nuclease (Cas9/sgRNA) rAAV6-mediated HR at β-globin (HBB) locus HSPCs. We identified that by transducing HSPCs with rAAV6 post-electroporation, there was...
ConspectusCationic polymers have been investigated as nonviral vectors for gene delivery due to their favorable safety profile when compared viral vectors. However, are limited by poor efficacy in inducing expression. The physicochemical properties of cationic enabling successful expression order improve efficiency and safety. Studies over the past several years focused on five possible rate-limiting processes explain differences expression: (1) endosomal release, (2) transport within...
Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the CF transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction most common pathogenic mutation, there are many other mutations throughout gene. An autologous airway stem cell therapy in which CFTR cDNA precisely inserted into locus may enable development durable cure for almost all patients, irrespective causal mutation. Here, use CRISPR-Cas9 and two...
A "universal strategy" replacing the full-length
Rationale: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis response and rebound congestion, caused by α-adrenoceptor mediated down-regulation desensitization response.Objectives: We evaluated if can be reversed fluticasone propionate, the relative α1- α2-adrenoceptor components using α1-antagonist prazosin.Methods: In a randomized, double-blind, placebo-controlled, crossover design, 19 healthy subjects received 200 μg three times day for 14 days,...
Developing improved cationic polymer-DNA polyplexes for gene delivery requires understanding of DNA transport from endosomes into the nucleus. Using a FRET-capable oligonucleotide molecular beacon (OMB), we monitored intact to cell organelles. We observed that effective (jetPEI) and ineffective (G5 PAMAM) vectors, fraction cells displaying OMB in cytosol (jetPEI ≫ G5 quantitatively predicted expressing transgene PAMAM). Intact delivered with PAMAM confined could be released by subsequent...
Abstract There is no consensus regarding optimal interpretative criteria (IC) for Fluorine-18 fluorodeoxyglucose (FDG) Positron Emission Tomography – Computed (PET-CT) response assessment following (chemo)radiotherapy (CRT) head and neck squamous cell carcinoma (HNSCC). The aim was to compare accuracy of IC (NI-RADS, Porceddu, Hopkins, Deauville) predicting loco-regional control progression free survival (PFS). All patients with histologically confirmed HNSCC treated at a specialist cancer...
Modulator agents that restore cystic fibrosis transmembrane conductance regulator (CFTR) function have revolutionized outcomes in fibrosis, an incurable multisystem disease. Barriers exist to modulator use, making local CFTR gene and cell therapies attractive, especially the respiratory tract. We used CRISPR gene-correct upper airway basal stem cells (UABCs) show durable engraftment into recipient murine epithelium. Interestingly, human recapitulate vivo organization differentiation of sinus...
In vivo gene therapy targeting hematopoietic stem cells (HSCs) holds significant therapeutic potential for treating hematological diseases. This study uses adeno-associated virus serotype 6 (AAV6) vectors and Cre recombination to systematically optimize the parameters effective in HSC transduction. We evaluated various genetic architectures delivery methods of AAV6, establishing an optimized protocol that achieved functional more than two-thirds immunophenotypic HSCs. Our findings highlight...
To study the prognostic value of rapid-acquisition adenosine stress-rest myocardial perfusion scintigraphy (MPS) on a gamma camera using multipinhole collimation and cadmium-zinc-telluride (CZT) detectors. The secondary aim was to assess diagnostic accuracy technique compared with invasive coronary angiography.Retrospective analysis 1109 consecutive patients undergoing MPS in routine clinical setting high-efficiency camera. acquisition, performed standard injection 550 MBq...
Cationic gene delivery agents (vectors) are important for delivering nucleotides, but also responsible cytotoxicity. polymers (L-PEI, jetPEI, and G5 PAMAM) at 1× to 100× the concentrations required translational activity (protein expression) induced same increase in plasma membrane current of HEK 293A cells (30–50 nA) as measured by whole cell patch-clamp. This indicates saturation cationic polymers. The increased currents not reversible over 15 min. Irreversibility on this time scale is...
Genome-editing technologies that enable the introduction of precise changes in DNA sequences have potential to lead a new class treatments for genetic diseases. Epidermolysis bullosa (EB) is group rare disorders characterized by extreme skin fragility. The recessive dystrophic subtype EB (RDEB), which has one most severe phenotypes, caused mutations COL7A1. In this study, we report gene-editing approach ex vivo homology-directed repair (HDR)-based gene correction uses CRISPR-Cas9 system...
Summary Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non‐allergic unified airway. The factors associated airway dysfunction in CRSwNP are not fully understood. Objective To assess impact disease on lower CRSwNP. Methods Fifty‐seven patients underwent spirometry, endoscopy, exhaled nitric oxide, methacholine bronchial challenge, blood sampling for total IgE, eosinophil count and radioallergosorbent testing...
Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted dose ranging study in asthma and persistent to evaluate if intranasal corticosteroids exhibit sparing of inhaled corticosteroid.Twenty five participants were randomized receive two weeks 100 microg/day (Low dose) or 500 (High fluticasone propionate both with placebo; 200 (Combined) double-blind cross-over fashion.Low produced shift 1.20 doubling-dilutions (95% CI, 0.63, 1.77);...
The desire to synthesize soft supramolecular structures with size scales similar biological systems has led work in assembly of polymeric nanomaterials. Recent advances the isolation generationally homogenous poly(amidoamine) (PAMAM) dendrimer enables their use as quantized building blocks. Here, we report into precise nanoclusters. In this work, click-functional ligands are stochastically conjugated monomeric generation 5 PAMAM and separated via reverse-phase HPLC isolate dendrimers numbers...