A5023156464- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Connective tissue disorders research
- Cardiac electrophysiology and arrhythmias
- Viral gastroenteritis research and epidemiology
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Bone fractures and treatments
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Orthopaedic implants and arthroplasty
- Bacterial Genetics and Biotechnology
- Sexual Differentiation and Disorders
- Antimicrobial Resistance in Staphylococcus
- Neuroscience and Neural Engineering
- Herpesvirus Infections and Treatments
- Muscle Physiology and Disorders
- Animal Virus Infections Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Adenosine and Purinergic Signaling
- Xenotransplantation and immune response
- Organ and Tissue Transplantation Research
- Phagocytosis and Immune Regulation
Children's Medical Research Institute
2015-2025
Sydney Children’s Hospitals Network
2016-2025
The University of Sydney
2015-2025
Children's Hospital at Westmead
2005-2020
Westmead Institute
2016
Children's Hospital
2013
Westmead Hospital
2005
Cardiac conduction occurs in an electrical syncytium of excitable cells connected by gap junctions. Disruption these electrophysiological properties causes slowing or block. Depending on the location affected within heart, this has potential to result clinical syndromes such as atrioventricular With a view developing gene therapy strategies for repairing cardiac defects, we sought establish whether phenotype fibroblasts can be modified transfer produce capable excitation and...
Abstract To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or approved worldwide. Our database brings together global information on activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators sponsors. This review presents our analysis of that, the best knowledge, being performed As November 2017 update, we entries 2597 undertaken in 38 countries. We...
AAVs isolated from human liver are tropic for hepatocytes in vivo, but this phenotype becomes attenuated after passage culture.
Recombinant adeno-associated viruses (rAAVs) have emerged as one of the most promising gene therapy vectors that been successfully used in pre-clinical models heart disease. However, this has not translated well to humans due species differences rAAV transduction efficiency. As a result, search for human cardiotropic capsids is major contemporary challenge. We capsid-shuffled library perform directed evolution iPSC-derived cardiomyocytes (hiPSC-CMs). Five candidates emerged, with four...
Directed evolution of natural AAV9 using peptide display libraries have been widely used in the search for an optimal recombinant AAV (rAAV) transgene delivery across blood-brain barrier (BBB) to CNS following intravenous ( IV) injection. In this study, we a different approach by creating shuffled rAAV capsid library based on parental serotypes 1 through 12. Following selection mice, 3 novel variants closely related AAV1, AAV-BBB6, AAV-BBB28, and AAV-BBB31, emerged as top candidates. direct...
Gene therapies and associated technologies are transforming biomedical research enabling novel therapeutic options for patients living with debilitating incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials diseases of multiple organs, such as the liver nervous system. Despite successes toward development bioengineered AAV variants improved transduction primary human tissues cells, that can...
The development of leukemia as a consequence vector-mediated genotoxicity in gene therapy trials for X-linked severe combined immunodeficiency (SCID-X1) has prompted substantial research effort into the design and safety testing integrating vectors. An important element vector is selection evaluation promoter-enhancer elements with sufficient strength to drive reliable immune reconstitution, but minimal propensity enhancer-mediated insertional mutagenesis. In this study, we set out explore...
Despite the availability of life-saving corticosteroids for 70 years, treatment adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy an attractive possibility monogenic adrenocortical disorders such as congenital hyperplasia; however, requires further development gene transfer/editing technologies knowledge target progenitor cell populations. Vectors based on adeno-associated virus are leading system direct
Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of numerous inherited and acquired neurological conditions. Therefore, efficient stable gene delivery to these postmitotic cells has significant therapeutic potential. Among contemporary vector systems capable neuronal transduction, only those based on herpes simplex virus have been extensively evaluated PNS neurons. We therefore investigated transduction performance recombinant adeno-associated type...
Barcoded vectors are promising tools for investigating clonal diversity and dynamics in hematopoietic gene therapy. Analysis of clones marked with barcoded requires accurate identification potentially large numbers individually rare barcodes, when the exact number, sequence identity abundance unknown. This is an inherently challenging application, feasibility using contemporary next-generation sequencing technologies unresolved. To explore this potential application empirically, without...
Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with aim developing novel variants enhanced tropism for specific cell types, decreased seroreactivity, and increased manufacturability. Selection based directed evolution rely generation highly variable libraries using methods such as DNA-family shuffling, a technique reliant stretches high DNA...
Genome editing technology has immense therapeutic potential and is likely to rapidly supplant contemporary gene addition approaches. Key advantages include the capacity directly repair mutant loci with resultant recovery of physiological expression maintenance durable effects in replicating cells. In this study, we aimed a disease-causing point mutation ornithine transcarbamylase (OTC) locus patient-derived primary human hepatocytes vivo at therapeutically relevant levels.Editing reagents...
Objective: To report the outcome of gene therapy in an infant with X-linked severe combined immunodeficiency (SCID-X1), which typically causes a lack T and natural killer (NK) cells. Design setting: Ex-vivo culture transfer procedures were performed at The Children's Hospital Westmead, Sydney, NSW, March 2002. Follow-up to 2005 (36 months) is available. Patient: A 9-month-old male confirmed SCID-X1 (including complete absence cells) NK+ phenotype (a less common variant SCID-X1), no...
Modification of electrical conduction would be a useful principle to recruit in preventing or treating certain arrhythmias, notably ventricular tachycardia (VT). Here we pursue novel gene transfer approach modulate by reducing gap junctional intercellular communication (GJIC) and hence potentially modify the arrhythmia substrate. The ultimate goal is develop nondestructive uncouple zones slow focal transfer. Lentiviral vectors encoding connexin43 (Cx43) internal loop mutants were produced...
Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells local soft tissues may also take on an osteogenic phenotype. Myoblasts known adopt a gene program upon treatment with morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their capacity relative other progenitor types is unclear. further hypothesized sensitivity of BMP-2 would correlate BMP receptor expression. directly compared myoblastic murine cell lines...
ABSTRACT Conserved motif C, identified within members of the major facilitator superfamily (MFS) transport proteins that mediate drug export, was examined in tetracycline resistance efflux protein TetA(K) from Staphylococcus aureus ; C is contained transmembrane segment 5. Using site-directed mutagenesis, importance conserved glycine (G151, G155, G159, and G160) proline (P156) residues this investigated. Over 40 individual amino acid replacements were introduced; however, only alanine serine...
Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of a number debilitating inherited and acquired neurological conditions. The lack effective treatments for many such conditions provides strong rationale exploring novel therapeutic approaches, including gene therapy. Friedreich ataxia (FRDA), neuropathy, is progressive neurodegenerative disease associated with loss large from dorsal root ganglia. Because mouse model this well-characterized has been...