A5064778097- CAR-T cell therapy research
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Nerve injury and regeneration
- Adrenal Hormones and Disorders
- Autoimmune and Inflammatory Disorders Research
- SARS-CoV-2 and COVID-19 Research
- Viral Infectious Diseases and Gene Expression in Insects
- Peroxisome Proliferator-Activated Receptors
- Adenosine and Purinergic Signaling
- Neurogenesis and neuroplasticity mechanisms
- Viral Infections and Immunology Research
- Organoselenium and organotellurium chemistry
- T-cell and B-cell Immunology
- Acute Lymphoblastic Leukemia research
- Pharmacological Effects and Assays
- Protein Tyrosine Phosphatases
- Biotin and Related Studies
- Immunodeficiency and Autoimmune Disorders
- Rabbits: Nutrition, Reproduction, Health
- Biosimilars and Bioanalytical Methods
- Selenium in Biological Systems
- Monoclonal and Polyclonal Antibodies Research
Great Ormond Street Hospital
2020-2024
University College London
2015-2024
National Health Service
2022
October 6 University
2020
University of Bristol
2014
University of Washington
1956
The Ohio State University
1948
Cerebral Dopamine Neurotrophic Factor (CDNF) and Mesencephalic Astrocyte-derived factor (MANF) are members of a recently discovered family neurotrophic factors (NTFs). Here, we used intranigral or intrastriatal lentiviral vector-mediated expression to evaluate their efficacy at protecting dopaminergic function in the 6-OHDA model Parkinson's disease (PD). In contrast well-studied Glial-Derived (GDNF), no beneficial effects were demonstrated by striatal overexpression either protein....
Can selenium (Se) independent, epididymal-specific glutathione peroxidase 5 (GPX5) protect CHO-K1 cells from oxidative damage and, more specifically, lipid peroxidation and DNA mutation?CHO-K1 expressing GPX5 have increased resistance to challenge decreased levels of the downstream lesion 8-oxo-7,8-dihydroguanine (8-oxodG) compared with control cells.GPX5 associates sperm during transit epididymis, has been postulated peroxide-mediated attack. However, its function as an active questioned...
Heterozygous mutations in CTLA-4 result an inborn error of immunity with autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications allogeneic hematopoietic stem transplantation. Here, we designed homology-directed repair (HDR) editing strategy that inserts cDNA into first intron genomic locus primary human cells. This resulted regulated expression CD4 + cells, functional studies demonstrated CD80 CD86...
One of the striking characteristics adrenalectomized animal and Addisonian patient is a well-known susceptibility to infection. Numerous attempts study effect adrenal insufficiency upon development immunity has resulted in conflicting data. Interest relation cortical hormones release antibody globulin experimental animals been revived recent years by work Dougherty, White associates (1945, 1946) These authors have noted an enhancement immune titers treated with or adrenotrophic fractions...
X-linked lymphoproliferative disease is a rare inherited immune disorder, caused by mutations or deletions in the SH2D1A gene that encodes an intracellular adapter protein SAP (Slam-associated protein). essential for mediating several key processes and system - T cells particular are dysregulated its absence. Patients present with spectrum of clinical manifestations, including haemophagocytic lymphohistiocytosis (HLH), dysgammaglobulinemia, lymphoma autoimmunity. Treatment options limited,...
Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive disease caused by bi-allelic loss-of-function mutations in ADA2. Treatment with anti-TNF effective for the autoinflammatory and vasculitic components but does not correct marrow failure or immunodeficiency; anti-drug antibodies cause loss efficacy over time. Allogeneic haematopoietic stem cell transplantation may be curative, graft versus host remains a significant concern. Autologous gene therapy would therefore...
Abstract Background X-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies hematopoietic stem cell transplant (HSCT). However, this cohort particularly susceptible the chemotherapeutic regimens acutely affected by graft-vs-host (GvHD), driving poor long-term survival in...
Chimeric antigen receptor (CAR) T-cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate CAR into alpha constant (TRAC) locus take advantage endogenous promoter and regulatory elements expression. This used adeno-associated viral (AAV) vectors based on AAV6 deliver donor template encoding construct. Since original publication, improvements have been made this targeted integration technique,...
X-linked lymphoproliferative disease is an immunodeficiency arising from mutations in the SH2D1A gene encoding SAP, a key regulator of immune function expressed T cells, natural killer, and killer cells. Haemopoietic stem-cell transplantation curative, we have shown proof concept haemopoietic therapy mouse model. Preliminary data suggests that adoptive transfer cells corrected using lentiviral can correct defects. However, targeted editing may allow for physiologically regulated SAP...
Background: Heterozygous mutations in CTLA4 result an inborn error of immunity (IEI) (also known as primary immunodeficiency) with a severe clinical phenotype. Autologous T cell gene therapy may offer cure without the immunological complications allogeneic stem transplantation. The mutational landscape and requirement for tight regulation make viral addition approaches unappealing. Gene editing strategies permit alteration while retaining endogenous control machinery. Aims: We set out to...