An Interview with University of Oxford Professor Matthew Wood

Having (virtually) been introduced to professor Matthew Wood at a medical science event hosted by Somerville College Oxford in late 2020, I was blown away by his fantastic research into the use of gene therapies for degenerative diseases. Furthermore, professor Wood was instrumental in the establishment of the UK’s new Nucleic Acid Therapy Accelerator (NATA). I took this opportunity to gain more insight into NATA and researchers' hopes for the future of clinical impactful gene therapies.

Tell us a little about yourself and your positions at the University of Oxford and NATA.

Hello, my name is professor Matthew Wood F.Med.Sci. I graduated in medicine from the University of Cape Town, working in clinical neuroscience before gaining a doctorate in physiological sciences from the University of Oxford. I’m currently professor of neuroscience in the department of paediatrics at the University of Oxford as well as deputy head of the medical sciences division responsible for innovation with an international profile. I also co-lead several research initiatives. I direct the laboratory of RNA biology and neuromuscular disease, investigating development of RNA-based medicines for neuromuscular disease, and my research focuses on the development of advanced generation antisense oligonucleotides for Duchenne muscular dystrophy and related neuromuscular conditions. I also serve as director of MDUK Oxford Neuromuscular Centre and director of the Oxford Harrington Rare Disease Centre. I also serve as a non-executive director of the University of Oxford’s technology transfer organisation, Oxford University Innovation (OUI)). Having initiated NATA's development, I provided overarching leadership and strategic direction during the initial development phase as interim director from 2019 through the end of 2020. I am currently a member of its scientific advisory board.

Tell us about your gene therapy research and the technologies you use.

My research is in the field of gene therapy for degenerative disorders of the nervous system and muscle. The main focus is the investigation of novel therapeutic approaches utilising short nucleic acids to target messenger RNA. Targeting RNA has the potential to allow modification of the target transcript, reprogramming of endogenous genetic defects, or the targeting of specific disease alleles, all the while maintaining endogenous regulation of the target gene. The focus of our work over the last 20 years has been on oligonucleotide therapeutics and developing oligonucleotides and related technologies for gene correction, via exon skipping, in Duchenne muscular dystrophy (DMD) and related neuromuscular disorders. While the first exon skipping drug (eteplirsen) for DMD was approved by the FDA in 2016, a major effort has been in progress to develop second generation oligonucleotide drugs and particularly technologies to improve and/or target the delivery of oligonucleotide drugs to extra-hepatic tissues of interest. Our focus over the last decade has been twofold: first investigating peptide technologies for oligonucleotide delivery (now being developed by a company Pepgen, of which I was a cofounder) and second studying the biology of extracellular vesicles such as exosomes and developing an exosome-based nanotechnology platform for oligonucleotide and nucleic acid delivery (now being advanced by Evox Therapeutics, of which I was a cofounder).

Can you tell us more about NATA and what it aims to achieve?

NATA is a new UK scientific institute focusing on accelerating development of novel nucleic acid therapeutics, which will support state-of-the-art interdisciplinary research to solve cross-cutting scientific and technical barriers to nucleic acid drug development and delivery, through establishment of a NATA infrastructure hub and building partnerships and consortia to focus on a series of major nucleic acid therapeutics research challenges.

The Medical Research Council (MRC), as part of UK Research and Innovation (UKRI), is investing an initial £30m over four years to establish NATA and its scientific programmes. It is supported by an independent scientific advisory board of international experts from academia, industry, and the investor community and aims to become an internationally recognised research institute and major UK national infrastructure research facility.

The NATA is based at Harwell Campus, just outside Oxford, UK. It’s an excellent location as Harwell is a huge 710 acre research campus comprising commercial science and research clusters in life sciences and physical sciences. It is internationally renowned for innovation, high technology industry, and research. It is very well placed within the UK, as Oxfordshire has one of Europe’s most successful life sciences clusters with a track record in establishing and attracting world leading life sciences businesses. Oxfordshire is part of the UK’s "Golden Triangle," forming an area of significant economic growth and expertise in life sciences and health, alongside those of Cambridge and London. More information is available here.

What gene therapy technologies does NATA focus on?

NATA has an exclusive focus on non-viral nucleic acid therapeutics (i.e. oligonucleotide, RNAi, miRNA, mRNA etc). In particular, there is a focus on some of the major barriers to success for this therapeutic class including delivery and targeting to specific organs/tissues, and manufacturing, and working on innovative solutions to these barriers. As a national UK facility, it was important for NATA to contribute to work to develop anti-viral therapies for COVID-19. Successful work had been done previously to develop anti-viral nucleic acid therapies, including for SARS-1, and therefore this provided a solid platform to develop an anti-viral for COVID-19. Work is being done with teams at Oxford and the Crick Institute in London.

Finally, what is your vision for gene therapy and its future in the clinic?

While much of the current focus for gene and nucleic acid therapy is on genetically well-defined rare diseases the future vision is for these therapies to be available for the common diseases which are major causes of morbidity and mortality including cancer, heart disease, and dementia. This will require that nucleic acid therapies can be manufactured in high volumes and are cost-effective, and therefore manufacturing innovations to make this possible are essential. Safety is also crucial, and an increasing ability to target these drugs effectively to only the cells and tissues of interest will provide the precision medicines of the future – precision in terms of delivery as well as in terms of genetic target.

Dr. Mulholland is a postdoctoral research scientist in cancer genetics and Junior Research Fellow (Somerville College) at the University of Oxford. He is a member of the ASGCT Communications Committee.