Matthew Wood

Research Focus

RNA targeted gene therapy for degenerative disorders of the nervous system and muscle. Targeting RNA has the potential to allow modification of the target transcript, reprogramming of endogenous genetic defects or the targeting of specific disease alleles, while maintaining endogenous regulation of the target gene. Current work is investigating antisense oligonucleotides for splice correction in Duchenne muscular dystrophy; novel chemistries and ligand targeting to skeletal and cardiac muscles. In addition, the potential of post-transcriptional gene silencing, RNA interference (RNAi), is being investigated for the silencing of target genes and mutant alleles both in muscle and in the nervous system. The current focus here is the targeted silencing dominant mutant alleles associated with the neurodegenerative disorders Parkinson’s disease and spinocerebellar ataxia.

Publications

1. Jagannath, A. and Wood, M.J.A. (2008). Localization of double-stranded siRNA to cytoplasmic GW-Bodies is Ago2-dependent and induces upregulation of GW182. Molecular Cell Biology 20, 521-529.
2. Ivanova, G.D., Arzumanov, A., Abes, R., Yin, H., Wood, M.J.A., Lebleu, B. and Gait, M.J. (2008). Improved cell-penetrating peptide-PNA conjugates for splicing redirection in HeLa cells and exon skipping in mdx mouse muscle. Nucleic Acids Research 6(20), 6418-6428.
3. Yin, H.F., Moulton, H.M., Seow, Y., Boyd, C., Iverson, P. and Wood, M.J.A. (2008). Cell-penetrating peptide-conjugated antisense oligonucleotides restore systemic muscle and cardiac dystrophin expression and function. Human Molecular Genetics 17(24), 3909-3918.
4. Trulzsch, B., Garnett, C., Davies, K.E. and Wood, M.J.A. (2007). Knockdown of SMN by RNA interference induces apoptosis in differentiated P19 neural stem cells. Brain Research 1183, 1-9.
5. Yin, H., Lu, Q. and Wood, M.J.A. (2007). Peptide nucleic acids and PNA conjugates for dystrophin exon skipping in the mdx mouse. Molecular Therapy 16(1), 38-45.
6. Wood, M.J.A., Yin, H. and McClorey, G. (2007). Modulating the expression of disease genes with RNA-based gene therapy. PLoS Genetics 3(6):e109
7. Trulzsch, B., Davies, K. and Wood, M.J.A. (2004). Survival of motor neuron gene downregulation by RNAi: towards a cell culture model of spinal muscular atrophy. Brain Research Molecular Brain Research 120, 145-50.
8. Wood, M.J.A., Trulzsch, B., Abdelgany, A., Beeson, D. (2003). Therapeutic gene silencing in the nervous system. Human Molecular Genetics, 12, R279-84.
9. Abdelgany, A., Wood, M.J.A., Beeson, D. (2003) Allele-specific silencing of a pathogenic mutant acetylcholine receptor subunit by RNA interference. Human Molecular Genetics, 2003 12, 2637-44.
10. Phylactou, L.A., Darrah, C. and Wood, M.J. (1998). Ribozyme-mediated trans-splicing of a trinucleotide repeat. Nature Genetics 18, 378-81.

Key lab techniques: Splice correction; RNAi related methods; neural cell culture

Lab contact: matthew.wood@dpag.ox.ac.uk

Lab website: http://users.ox.ac.uk/~mjawood/; http://www.dpag.ox.ac.uk/academic_staff/matthew_wood