Professor Matthew Wood
I am an RNA biologist and neuroscientist, with a principal focus on the study and development of nucleic acid based therapies for neurological and neuromuscular disease. I do this through my own laboratory, the Laboratory of RNA biology and Neuromuscular Disease, and as Director of the MDUK Oxford Neuromuscular Centre and of the Oxford Harrington Rare Disease Centre, the latter a trans-Atlantic partnership with the Harrington Discovery Institute, Cleveland, USA.
Over the last two decades, a major focus has been development of oligonucleotide-based therapy for Duchenne muscular dystrophy (DMD). This included pre-clinical and early clinical development of Eteplirsen, a drug subsequently developed by Sarepta Therapeutics that in 2016 received FDA approval as the first ever disease-modifying oligonucleotide treatment for DMD. Subsequent work has focused on related neuromuscular targets and on discovery of peptide-based oligonucleotide drug delivery technologies, leading to a new company Pepgen developing peptide-oligonucleotide technology for clinical application in neuromuscular diseases.
As part of our programme to develop new methods for nucleic acid drug delivery, studies beginning in 2007 to bioengineer exosomes for brain-targeted RNA therapy led to the new field of extracellular vesicle (EV) therapeutics. Evox Therapeutics, a company founded in 2016, continues to exploit the therapeutic potential of EV technology. I was also in 2019 the Founder and first director of the UK Nucleic Acid Therapy Accelerator (NATA), a major UK research centre to support the development of nucleic acid therapeutics.
I serve on the Board of University of Oxford technology transfer company, Oxford University Innovation. I have published over 300 papers, my h-index is 86, and I was a Web of Science highly cited researcher in 2020. I am a Fellow of the Academy of Medical Sciences.
Find out more about Professor Wood's work.
Development of oligonucleotide therapy for the neuromuscular disease Duchenne Muscular Dystrophy
I have advanced the pre-clinical chemistry and biology of first-generation antisense oligonucleotides for treatment of DMD in partnership with Sarepta Therapeutics, demonstrating proof-of concept in Phase I/II clinical trials with a compound that, in 2016, received FDA approval as the first ever disease-modifying treatment for DMD. I have also led development of related first generation oligonucleotide technologies for DMD.
- Kinali M et al. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009, 8(10):918-28 doi: 10.1016/S1474-4422(09)70211-X.
- Cirak S et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet. 2011, 13; 378(9791):595-605. doi: 10.1016/S0140-6736(11)60756-3.
- Goyenvalle A et al. Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers. Nature Medicine. 2015, 21(3):270-5 doi: 10.1038/nm.3765.
- Han G et al. Hexose enhances oligonucleotide delivery and exon skipping in dystrophin-deficient mdx mice. Nature Communications 2016,11;7:10981. doi: 10.1038/ncomms10981.
Fundamental studies to investigate exosome biology and development of novel exosome engineering therapies
I have led paradigm shifting studies to establish the field of EV therapeutics, a disruptive technology exploiting the inherent properties of natural nanoparticles known as exosomes, for tissue-targeted RNA therapy. This work was highlighted in 2016 as one of the twenty most influential and highly cited Nature Biotechnology publications in the first 20 years of that journal.
- Alvarez-Erviti L et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nature Biotechnology. 2011, 29(4):341-5. doi: 10.1038/nbt.1807
- El-Andaloussi S et al. Exosome-mediated delivery of siRNA in vitro and in vivo. Nature Protocols. 2012, 7(12):2112-26. doi: 10.1038/nprot.2012.131.
- Heusermann W et al. Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER. J Cell Biol. 2016, 25;213(2):173-84. doi: 10.1083/jcb.201506084.
- Olivier G. de Jong et al. A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA. Nature Communications. 2020; 11: 1701. doi: 10.1038/s41467-020-14977-8.
Fundamental studies to investigate peptide chemistry and develop novel oligonucleotide therapies for neurological and neuromuscular disease
I have discovered next generation therapeutic oligonucleotides, including novel peptide chemistries to enhance disease-modifying treatment of the neuromuscular disease DMD and related disorders including myotonic dystrophy.
- Hammond SM et al. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy. Proc Natl Acad Sci U S A. 2016, 113(39):10962-7. doi: 10.1073/pnas.1605731113.
- Klein AF et al. Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice. J Clin Invest. 2019, 129(11):4739-4744. doi: 10.1172/JCI128205.