Our research focuses on the pre-clinical development of gene therapies for neuromuscular diseases, in particular the muscular dystrophies based on gene addition, endonuclease-mediated gene editing, antisense oligonucleotide (AO)-induced exon skipping and gene silencing. This involves the engineering and testing of viral (AAV, lentivirus) and non-viral (plasmid, oligonucleotide) gene therapy vectors in pre-clinical models in the areas of Duchenne muscular dystrophy (DMD), facioscapulohumeral dystrophy (FSHD) and oculopharyngeal muscular dystrophy (OPMD).

Research involves vector, AO and endonuclease design, their engineering and production, and evaluation of therapeutic efficacy in cell culture and transgenic disease models. The work is focused in the following areas: (i) Development of antisense therapeutics to modulate RNA splicing to restore dystrophin expression for DMD; (ii) Exploration of means to enhance delivery of AOs; (ii) Optimisation and in testing of AOs to knockdown toxic DUX4 expression in models of FSHD; (iii) Targeting of specific genes with AOs and catalytically-inactive CRISPR/Cas9 tethered to transcriptional activators and inhibitors to modulate muscle fibrosis and myogenesis; (iv) Development of endonucleases for editing of the dystrophin gene that would have high patient applicability; (v) Development of combination therapies to address the multifactorial nature of muscular dystrophy; and (vi) Optimisation of AAV vector construct for DMD and OPMD.

We interact well with industry and have seen some of patented therapies enter clinical trial. Future work will concentrate on further pre-clinical development of therapies with the prospect of future clinical testing through collaboration with existing pharmaceutical partners.

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Professor Popplewell is the Director of the Centre for Biomedical Sciences

CBMS

I have published more than 40 research articles in peer-reviewed journals, contributed chapters to three different books, and have recently co-authored a textbook on Gene Therapy (publication in February 2020).  As of January 2020, I have a citation (h) index of 15 and an average of 23.94 citations per publication. A key Lancet Neurology paper has been cited 261 times.

My research has resulted in the filing of six patents for intellectual protection. Two of these have been fully granted. These patents have been licensed to US pharma companies. Milestone payments from a clinical trial of one of the patents have recently been paid to College.

REF Impact casestudy - Treating Duchenne Muscular Dystrophy

I have been fortunate to be involved in academic-related activities beyond the HE sector to (i) effectively disseminate my research and (ii) contribute to the gene therapy field at large . These activities include:

• Delivering invited presentations at a number of parent/patient conferences (Nov 2013, Oct 2016, Nov 2019)
• Organising patient/parent lab visit days (Jul 2017, Feb 2019)
• Being Interviewed by Society of Physiology to provide a lay video on applications of gene editing (Nov 2016)
• Appearing on BBC Radio Surrey to talk about my research (Aug 2015)
• Taking part in Facebook Q&A session organised by a charity on my research (Feb 2018)
• Being invited to present my research on number of occasions at College-held public event on Rare Diseases (Feb 2015, Feb 2020).
• Being an elected Board member of British Society of Gene and Cell Therapy (BSGCT) since 2018, in particular sitting on the Public Engagement Sub-Committee that acts to engage and disseminate research findings to general public
• Being an invited member of the External Scientific Committee of Duchenne Parent Project Spain
• Being invited to make a video for use in teaching A-level biology in schools
• Being interviewed by students from ACS, Egham (March 2018)
• Presenting and participating in an A-Level Science Symposium at Stroudes College, Egham (March 2018)

On the basis of my research, I was invited to join the MDEX Consortium, which is a group of high-profile UK researchers working in the field to allow effective collaboration and exchange of ideas.

Having contributed to the writing of the application to secure the grant, I am part of the Management Committee of a current European Collaboration in Science and Technology (eCOST) Action, I hold responsibility for awarding funds to scientists from Inclusiveness Target Countries (ITC) to facilitate their attendance at international conferences.