Nucleic Acids
- +44 (0)1865 275413
- tom.brown@chem.ox.ac.uk
- http://www.browngroupnucleicacidsresearch.org.uk/
Tom Brown
Our focus is on the applications of chemically modified nucleic acids. Using X-ray crystallography and NMR we have studied the nature of base mispairing in DNA, the structure of DNA duplexes containing mutagenic lesions and the interaction of DNA with repair enzymes. We also design modified nucleic acids for diagnostic and therapeutic applications and have developed rapid methods for the identification of mutations in the human genome. The best example is Scorpions which are used to analyse genomic DNA at single base resolution. Scorpions were developed in collaboration with AstraZeneca spin-out DxS genotyping, and are used in companion diagnostics. They have led to the clinical use of cancer drugs which were previously rejected on the basis of limited efficacy.
A Scorpion kit is used to group patients on the basis of their KRAS mutation status; and as a result of this the drug Vectibix® was approved for the KRAS wild-type population. Similarly an EGFR kit is being used to establish the mutation status of non-small cell lung cancer tumours, to determine likely response to the drugs Iressa® and Tarceva®. The Scorpion technology has been acquired by Qiagen who obtained FDA approval of the KRAS kit in the US for use with the colorectal cancer drug Erbitux®.
We also work on the synthesis of DNA analogues for therapeutic applications including aptamers to target cancer cells with the aim of delivering drugs, and are developing CRISPR-based systems for cellular imaging and editing. We have developed a number of artificial DNA/RNA backbones that can be read through by polymerase enzymes. This led us to develop chemical methods of nucleic acid ligation and gene synthesis with the eventual aim of assembling therapeutic mRNAs on a large scale.
Lead Principal Investigator
Research Theme
Selected Publications
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Assembly of a biocompatible triazole-linked gene by one-pot click-DNA ligation.
Journal article
Kukwikila M. et al, (2017), Nat Chem, 9, 1089 - 1098
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An autonomous molecular assembler for programmable chemical synthesis.
Journal article
Meng W. et al, (2016), Nat Chem, 8, 542 - 548
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Reversible Ligation of Programmed DNA-Gold Nanoparticle Assemblies.
Journal article
Harimech PK. et al, (2015), J Am Chem Soc, 137, 9242 - 9245
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New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes.
Journal article
El-Sagheer AH. and Brown T., (2010), Proc Natl Acad Sci U S A, 107, 15329 - 15334
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Detection of PCR products using self-probing amplicons and fluorescence.
Journal article
Whitcombe D. et al, (1999), Nat Biotechnol, 17, 804 - 807
Latest News
A tempting new target for cancer therapy
15 October 2019
Kristijan Ramadan and his group published a new article in The EMBO Journal today. The article adds new detail to the story of how our cells repair damage to our DNA.
New 'molecular fibres' may help cells repair DNA
25 March 2019
Research by the DNA Damage & Disease research group has for the first time observed molecular fibres that may hold together sections of broken DNA in mitosis.
Medical Research Council grant success for Peter McHugh
8 February 2018
Associate Professor Peter McHugh of the Department of Oncology has been awarded a 4 year grant from the Medical Research Council.
Peter McHugh awarded CRUK grant to investigate how cancel cells resist treatment
6 February 2018
The 5-year programme award will support research on the DNA repair mechanisms that protect cancer cells from therapy, informing the development of future therapies.