A5039254563- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Neuroblastoma Research and Treatments
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- MicroRNA in disease regulation
- Cutaneous Melanoma Detection and Management
- Lipid Membrane Structure and Behavior
- Transgenic Plants and Applications
- Cell death mechanisms and regulation
- Retinoids in leukemia and cellular processes
- Neonatal Respiratory Health Research
- Tracheal and airway disorders
- Monoclonal and Polyclonal Antibodies Research
- Polyoxometalates: Synthesis and Applications
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Marine Sponges and Natural Products
- Cystic Fibrosis Research Advances
- Infant Nutrition and Health
- Neuroscience of respiration and sleep
- Intracerebral and Subarachnoid Hemorrhage Research
- melanin and skin pigmentation
- Biotin and Related Studies
University College London
2014-2024
Great Ormond Street Hospital
2017-2024
Formulations of cationic liposomes and polymers readily self-assemble by electrostatic interactions with siRNA to form nanoparticles which achieve efficient transfection silencing in vitro.However, the utility formulations vivo is limited due rapid clearance from circulation, their association serum proteins, as well systemic cellular toxicity.These problems may be overcome anionic but they provide challenges self-assembly efficiency.We have developed anionic, nanocomplexes utilizing...
Despite recent advances in the field of mRNA therapy, lack safe and efficacious delivery vehicles with pharmaceutically developable properties remains a major limitation. Here, we describe systematic optimisation lipid-peptide nanocomplexes for two murine cancer cell types, B16-F10 melanoma CT26 colon carcinoma as well NCI-H358 human lung bronchoalveolar cells. Different combinations lipids peptides were screened from an original nanocomplex formulation improved luciferase transfection vitro...
Abstract The authors aim to develop siRNA therapeutics for cancer that can be administered systemically target tumors and retard their growth. efficacy of systemic delivery with nanoparticles based on lipids or polymers is often compromised by rapid clearance from the circulation liver. Here, multifunctional cationic anionic nanoparticle formulations are described, termed receptor‐targeted nanocomplexes (RTNs), comprise peptides packaging into receptor‐mediated cell uptake, together confer...
Abstract Background Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels CFTR (cystic fibrosis transmembrane conductance regulator), gene mutated cystic fibrosis. By providing an infinite source epithelial (AECs), use human induced pluripotent stem (hiPSCs) could overcome some challenges studying ionocytes. However, production AEC epithelia containing from hiPSCs has proven difficult. Here, we present...
RAS proteins regulate cell division, differentiation, and apoptosis through multiple downstream effector pathways. Oncogenic variants are the commonest drivers in cancers; however, they also drive many benign lesions predisposing to malignancy, such as melanocytic nevi, thyroid nodules, colonic polyps. Reversal of these could reduce cancer incidence; effects oncogenic have been notoriously difficult target with pathway inhibitors. In this study, we show effective suppression currently...
In a wide range of neuroblastoma-derived lines oxovanadium compounds such as bis(maltolato)oxovanadium(IV) (BMOV) are cytotoxic. This is not explained by oxidative stress or inhibition ion channels. Genotoxicity unlikely given that p53 response absent and p53-mutant also sensitive. Cytotoxicity inhibited N-acetyl cysteine glutathione ester, indicating BMOV action sensitive to cytoplasmic redox thiol status. Significantly, combining with synthesis greatly enhances BMOV-induced cell death....
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The 10th most common mutation, c.3178-2477C>T (3849+10kb C>T), involves a cryptic, intronic splice site. This mutation was corrected CF primary cells homozygous for this delivering pairs of guide RNAs (gRNAs) with Cas9 protein ribonucleoprotein (RNP) complexes that introduce double-strand breaks to flanking sites excise 3849+10kb C>T followed DNA repair non-homologous end-joining pathway, which...
Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display
Abstract Airway mucus is a major barrier to the delivery of lipid‐based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor‐Targeted Nanocomplexes (RTN), comprise mixtures cationic lipids and bifunctional peptides with receptor‐targeting nucleic acid packaging properties. The aim this study improve mucus‐penetrating properties siRNA mRNA RTNs by combining them low molecular weight alginate oligosaccharides, OligoG OligoM. Cationic formulated either become strongly...
Abstract Oxidovanadium complexes with organic ligands are well known to have cytotoxic or differentiating capabilities against a range of cancer cell types. Their limited use in clinical testing though has resulted largely from uncertainties about the long-term toxicities such complexes, due part speciation vanadate ions circulation. We hypothesised that more highly stable delivered using liposomes, may provide improved opportunities for oxidovanadium applications cancer. In this study we...
Retinoid treatment is employed during residual disease in neuroblastoma, where the aim to induce neural differentiation or death tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, CYP26 enzyme production liver, enhancing their own rapid metabolic clearance, while retinoid resistance cells themselves considered be due part increased production. Retinoic acid metabolism blocking agents...
Abstract Severe cases of congenital melanocytic naevi (CMN) are associated with substantial cutaneous and neurological morbidity an excess childhood mortality from melanoma. Effective treatments lacking. This mosaic disorder is caused most commonly by a heterozygous oncogenic variant NRAS c.181C>A, p.(Q61K). As has multiple downstream effectors we have sought to treat this disease precision genetic therapy rather than pathway inhibition, hypothesising that silencing the allele may...
Neuroblastoma (NB) is the most common malignant solid tumour in childhood and accounts for 15% of cancer deaths. High risk NB strongly correlated with MYCN amplification survival rate very low at approximately 30-50%. MYCN, a member MYC proto-oncogene family, an evolutionarily conserved bHLHZip transcription factor. controls various target genes that regulate essential cellular processes such as proliferation, cell growth, apoptosis differentiation certain tissues embryo, while it or absent...
Studies into the systemic delivery of siRNA to tumours with cationic nanoparticles often report problems rapid clearance from circulation, particularly liver. Our aim was optimize surface properties retain maximal transfection efficiency while achieving tumour specific transfection. Here we prepared and anionic receptor-targeted nanocomplexes (RTNs) compared them for their biophysical properties, biodistribution efficacy in MYCN silencing vitro vivo. RTN formulations comprised a mixture...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)