Genome Stability

Current research projects

• Pioneering application of gene editing to transplant using RNA (PAGETURNA)

  Several rare childhood diseases cause shortened life because of loss of vital blood production. Collectively called bone marrow failure syndromes, they show great potential for treatment with gene editing. Our research focus is to use mRNA methods to deliver gene editing to bone marrow haematopoietic stem cells (HSCs) to treat these patients. In particular, we have pioneered a technique called Prime Editing – which we can show has exquisite ability to correct genetic mutations in HSCs. In addition to getting Prime Editing to work in this difficult cell type, we have also improved the range of targets that can be edited using novel Prime Editors combinations. Finally, by manipulating DNA damage repair (DDR) in target cells, we can increase the efficiency of on-target editing, and reduce the number of deletions and insertions that cause editing to fail.

  Our short-term goal is to show in model systems that gene edited cells produce normal blood. Our medium-term goal is to use editing in HSCs of bone marrow failure syndrome patients, as a one-off, life-long curative therapy.

  The role of BLM, a gene mutated in Bloom Syndrome

  Bloom Syndrome is a rare inherited disorder that results in greater than 90% risk of developing cancer by the age of 25. The gene that causes Bloom Syndrome, called BLM, protects cells from cancer-causing mutations, hence affected individuals develop the same types of cancers as the general population, only much faster. We investigate the properties of the BLM gene product to understand how it protects us from cancer and may influence some forms of cancer treatment.

  Novel inhibitors of DNA repair as chemotherapy sensitisers in breast cancer

  Using our knowledge of how DNA repair proteins interact, we have designed new inhibitors that can sensitise cancer cells to chemotherapy. We are working to improve these inhibitors so that they may one day be useful in cancer treatment.

  The role of FANCM, a gene mutated in Fanconi anaemia

  Fanconi anaemia is an inherited disorder with greatly elevated risk of leukaemia and cancers. A causal gene called FANCM is a ‘tumour suppressor’. Our work is uncovering its tumour suppressor function: a complex function in repair of damage to our DNA. This study aims to understand how this protects us from cancer and may influence some forms of cancer treatment.