Marc Moore Email & Phone Number

Teesside Darlington

“Investigating Exon Skipping as a Therapeutic Approach to the treatment of Neurofibromatosis Type I” Phase B“Optimising non-bacterially generated NF1 cDNA and targeted non-viral particles for the treatment of NFI”- Lead a pipeline screening 6 extended antisense sequences, delivered In Vitro as an AAV transgenes; all outperformed current lead candidate. - Sub-cloned Lentivirus (LV) constructs capable of expressing antisense therapeutics, expanding viral delivery platforms.- Developed bi-cistronic reporter cassettes, for ASO candidates encoding luciferase and eGFP. Produced multiple AAVs from genetically engineered capsids. Enabling collaborators to undertake PK/ PD studies. - For the full length NF1 cDNA restoration pipeline, 5 NF1 cDNA candidates were designed for enzymatic DNA production as dbDNA or hpDNA, to enable expression profile analysis and DNA mutagenesis screening. - Applied with Prof. Popplewell and secured a Ph.D. studentship, with focus upon gene-editing as a therapeutic intervention for Becker Muscular Dystrophy (BMD). - Regularly presented internally at lab meetings and externally, most notably at the Child Tumour Foundation (CTF) Conference in Arizona. - Contributed to development of the NHC, as a research institute in its infancy. Procuring equipment to enhance research applications, liaising with external technical teams from companies to improve training for the PGR community, contributing internally to working risk assessment groups and best research practices.- Managed a small team of a Scientific experimental officer (SEO) and research assistants (RA), supporting in their experimental design, day-to-day research and technical training.

School Of Biological Sciences, Egham, Surrey

Research Project Affiliated with the University of Alabama Birmingham: Investigating Exon Skipping as a Therapeutic Approach to the Treatment of NF1- Lead multi-parameter antisense oligonucleotide (ASO) design, using in silico prediction tools identifying ESE distribution mRNA secondary structure and binding energetics. Identifying 7 ASO primary candidates for an exon target for NF1.- Developed efficacy assays based upon delivery of phosphonodiamidite oligomers with endoporter, PCR and densitometric analysis for ASOs, across control and genetically HEK293T cell lines to have representative NF1 patient mutations. - Identified 6 further ASO candidates including the current lead, from secondary iterative designs accounting for analysis of efficacy data. The approach and the candidates were subsequently patented; publication (Leier, Moore et al, 2022)- Continued assessment and development of ASOs to 3 further exon targets across the NF1 gene, with the outlook for further therapeutic exon-skipping or exon cryptic splice site silencing; publication (Ewad, K. E et al, 2021).- Sub-cloned and validated an Adeno-Associated Virus (AAV) constructs capable of expressing antisense sequencing. - Produced numerous AAV vectors, in roller bottle format, which were subsequently purified using AKTA Chromatography systems and concentrated. Including controls, fluorescent markers and therapeutic candidates.- Promising in vivo data from vectors secured a 12-month bridge fund and subsequent phase B, exploring further ASO sequences and AAV capsid screening. - Managed Lab maintenance, ordering and supervision of junior staff and students independently for 4 months during the pandemic.

Institute Of Child Health, Dubowitz Neuromuscular Centre

Sarepta Affiliated Research Project: Trans-differentiation of Patient Derived Fibroblasts, Assessing Exon-Skipping and Resultant Dystrophin Transcript Stability- Identified, procured and giga-prepped a lentiviral transfer plasmid encoding MyoD-Vp64.- Organised anonymised patient fibroblast samples into a database, in accordance with mutation type.- Produced and titred a large scale lentiviral production. - Estabilished a robust protocol for myogenic reprogramming of fibroblasts, with attention to: transduction, puromycin selection, differentiation culturing conditions, doxycycline induction and PMO treatments. - Confirmed differentiation with Immunohistochemistry (IHC), established QC for lentiviral transduction and puromycin selection using FACs analysis. - Re-programmed 15 primary patient fibroblast cultures, freezing pre/post transduction and pre/post selection prior to MyoD induced differentiation. - Post-transdifferentiation RNA and protein samples were harvested to assess for exon-skipping efficacy. - Co-supervision of an MSc student achieved a 2:1.- Lectured on UCL's MSc in Gene and Cell Therapy.

Institute Of Child Health, Dubowitz Neuromuscular Centre

Research Project: Genome Editing to Correct Duplication Mutations across the DMD gene. - Designed, sub-cloned and transfected SgRNA designs into HEK293T. - Estabilished and utilised TIDE and T7E1 assays, to assess NHEJ/ DNA cleavage. - Identified 5 SgRNA Candidates for development. - Utilised AMAXA electroporation for construct delivery to primary patient myoblasts. - FACs enriched cultures with anticipated genomic correction. - Established assays to assess genomic correction at cDNA and western blotting for protein levels. - Lectured on UCL MSc Gene and Cell Therapy Course. - Supervised 4 MSc Students for their research projects all were awarded 2:1 or higher. - Awarded a £2000 BRC Travel Grant for Research Dissemination and Project Development. FASEB Genome Engineering Conference: Cutting Edge Research and Applications

Doctor Of Philosophy - Phd, Genome Editing With Crispr/Cas9 To Correct Dmd Mutations

1St Bachelor Of Science - Bs (Hons), Biomedical Sciences, General