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This Centre is able to spearhead activities in this rapidly evolving area and play a major role in translational neuroscience in UCL.
The Genetic Therapy Accelerator Centre (GTAC) is led by Professor Francesco Muntoni, an Internationally recognised Paediatric Neurologist with dual appointments at UCL QS Institute of Neurology. He is director of the Dubowitz Neuromuscular Centre, at the UCL GOS Institute of Child Health and Great Ormond Street Hospital for Children. The foundation of the centre builds on his pioneering work in the first genetic therapies for neuromuscular disorders and the vision to apply this knowledge and experience to develop the next generation of genetic therapies for a range of neurological disorders. The revolution in genomics has led to an explosion of potential genetic targets as novel therapeutic targets.
In the last five years a number of extremely effective RNA and adeno-associated viral vectors (AAV) therapies have dramatically improved the outcomes for individuals affected by a range of neurological disorders, mostly affecting children. The focus of the centre is to harness the learning derived from these recent successes, mechanistic insight discovery, to early and late translational research and eventually regulatory approval, and apply it to a wider group of neurodegenerative disorders. The centre combines laboratory and clinical expertise focused on neurological, neuromuscular and neurodegenerative disorders, their mechanisms of disease and cutting-edge RNA and AAV gene therapy expertise, and foster cross-institutional collaborations between IoN QS and GOS ICH. Professor Muntoni, along with his team lead the research programmes in translational AAV and RNA therapeutics and provide expert advice and support to other departments at IoN QS and GOS ICH on translational genetic therapy developments from proof of concept, preclinical studies of efficacy and safety towards clinical translation.
The Centre develops links and synergies with other related activities including the Sigrid Rausing Trust Initiative, Dementia Research Institute, LMIC International Centre for Neuromuscular Diseases, Neurogenetics Therapies Programme, the two Biomedical Research Centres at IoNQS and GOSICH, and the genetic therapy Initiatives at the Zayed Centre for Research into Rare Disease in children.
- Adeno-Associated Vectors (AAV)
Adeno-associated viral vectors are a leading modality to deliver genetic therapies showing profound disease modifying impact on neurological disorders resulting in FDA approval for AAV gene therapies for spinal muscular atrophy, neurotransmitter disorder AADC deficiency and Duchenne muscular dystrophy. Dr Jo Ng leads preclinical translational AAV gene therapy development for neurological disorders such as dopamine transporter deficiency syndrome, infantile and juvenile parkinsonism and epileptic encephalopathy. Dr Ng collaborates with experts in clinical disease, genetic disease mechanism to develop clinically translatable AAV gene therapies. In addition Dr Ng works closely with AAV researchers to develop the technology to improve AAV transduction efficiency, selectivity and safety. Dr Ng is available on a monthly basis to discuss AAV projects with interested researchers to support queries from capsid selection, construct design, vector production to in vivo experimental design.
Project: AAV gene therapy for Tyrosine hydroxylase deficiency syndrome AAV gene therapy for DNAJC6 juvenile parkinsonism AAV gene therapy for Dopamine transporter deficiency syndrome. Peripheral Nerves made fluorescent with AAV vector.
- Related Publications:
- Gene Therapy for Dopamine Dyshomeostasis: From Parkinson's to Primary Neurotransmitter Diseases. Ng J, Barral S, Waddington SN, Kurian MA. Mov Disord. 2023 Jun;38(6):924-936. doi: 10.1002/mds.29416. Epub 2023 May 5. PMID: 37147851 Review.
- Dopamine Transporter Deficiency Syndrome (DTDS): Expanding the Clinical Phenotype and Precision Medicine Approaches. Ng J, Barral S, Waddington SN, Kurian MA. Cells. 2023 Jun 28;12(13):1737. doi: 10.3390/cells12131737. PMID: 37443770 Free PMC article.
- Reviews
- Novel AAV capsids (Dr John Counsell, Dr Killian Hanlon)
- Cell therapy for Dopamine Transporter deficiency syndrome (Dr Serena Barral, Prof Manju Kurian)
- Novel CNS promoters for AAV neurological gene therapy (Dr Riccardo Privolizzi, Professor Kevin Truong)
Collaborations: AAV gene therapy for devastating epileptic encephalopathy (Dr Raj Karda, Professors Stephanie Schorge, Simon Waddington, Cathy Abbott, Rocket Pharma ) AAV gene therapy for sodium channelopathy (Dr Juan Antinao-Diaz)
The centre runs regular surgeries to support researchers interested in developing or involved in AAV gene therapy or projects. Location: QSH For AAV drop in sessions, please contact Dr Jo Ng on j.ng@ucl.ac.uk to schedule a meeting. Dr Jo Ng Senior Research Fellow from Genetic Therapy Accelerator Centre, will be running regular surgeries to support researchers interested in developing or involved in AAV gene therapy projects. Jo has led preclinical AAV gene therapy projects in childhood neurological disorders. These have resulted in patent award, collaboration with industry partners, licensing agreements, orphan drug designation and clinical trial application. Her experience may help researchers consider translational aspects in AAV capsid selection, construct design, vector production, experimental design for preclinical efficacy and safety studies, approach to novel IP etc.
- RNA Therapies
Dr Sara Aguti is a molecular biologist with a profound interest in the development of RNA therapies to address unmet clinical needs. Sara holds a European PhD in Neuroscience from the University of Florence (Italy) and University College London. With over four years of postdoctoral experience at UCL Great Ormond Street Institute of Child Health, under the guidance of Professor Muntoni and Dr Haiyan Zhou, and one year at MINA therapeutics, Sara has acquired extensive expertise in RNA therapies, particularly in antisense oligonucleotide (ASO) therapy. During her post-doc she developed an ASO therapy for collagen VI related congenital muscular dystrophy, a rare disorder for which a cure is currently unavailable. Her work has generated several awards, including travel grants to present her research at national and international conferences, the WMS poster prize and the Dubowitz Prize in 2020. Additionally, she has filed three patents and received support from organizations like BRC, TIN, MDUK, and LifeArc for her translational research. Currently, Sara’s primary focus revolves around the development of ASO-peptide targeted delivery methods in various cells and tissues to overcome the challenges associated with ASO in vivo delivery.She is thrilled to have joined GTAC led by Professor Francesco Muntoni to support RNA therapy development for neurological and neuromuscular disorders at IoN. She will be available on a monthly basis to support ASO research at IoN. Her specific contributions include providing assistance in designing and chemically optimizing ASO sequences, optimizing ASO in vitro screening procedures, and refining in vivo delivery methods.
The centre runs regular surgeries to support researchers interested in developing or involved in RNA gene therapy or projects. Location: QSH . Dr Sara Aguti, a Senior Research Fellow at the Genetic Therapy Accelerator Centre, has experience in developing RNA therapies for childhood neuromuscular disorders using various approaches (ASO, siRNA and saRNA). Currently, her primary focus is on generating peptide-targeted delivery strategies for various cells and tissues to address the challenges associated with in vivo delivery. Sara will be conducting regular surgeries to support researchers in the design, development, and in vivo RNA therapy delivery. She will assist in the following areas. Mutation Suitability Assessment: Evaluating the suitability of specific mutations for the development of RNA therapies. Oligo Sequence Optimization: Optimizing oligonucleotide sequences to improve their efficiency and specificity through chemical modifications and the study of target RNA secondary structures. For RNA therapy drop in session, please contact Dr Sara Aguti on sara.aguti@ucl.ac.uk to schedule a meeting.
- In Vitro Oligo Screening: Assistance in designing of in vitro screening assays for oligos.
- In Vivo Oligo Delivery: Assisting in optimizing delivery methods to ensure efficient and effective delivery to the desired tissues or cells.
- Publications
- Coming soon
- Drop in Sessions
The centre runs regular surgeries to support researchers interested in developing or involved in AAV gene therapy or projects. Location: QSH For AAV drop in sessions, please contact Dr Jo Ng on j.ng@ucl.ac.uk to schedule a meeting. Dr Jo Ng Senior Research Fellow from Genetic Therapy Accelerator Centre, will be running regular surgeries to support researchers interested in developing or involved in AAV gene therapy projects. Jo has led preclinical AAV gene therapy projects in childhood neurological disorders. These have resulted in patent award, collaboration with industry partners, licensing agreements, orphan drug designation and clinical trial application. Her experience may help researchers consider translational aspects in AAV capsid selection, construct design, vector production, experimental design for preclinical efficacy and safety studies, approach to novel IP etc.
