Theme 2: Graft manipulation and gene editing

Current landscape

For many patients who need a transplant, there are a lack of suitably matched donors. Although cord blood can be used as an alternative donor source,  many cord units cannot be used because the content of stem cells is too low. Efforts are being made to expand stem cells in the laboratory but often, these approaches lead to loss of stem cell potential. Blood stem cells and other blood cells are important candidates for genetic manipulation, for example to correct an inherited gene defect or to provide a new function. However, there is no clear consensus on how to measure 'off target' effects, where unintended changes also occur.

THEME aims

Theme 2 aims to develop new methods for expanding blood stem cells that can be translated into clinical trials and to improve the specificity and safety of gene targeting approaches in blood cells.

OUR EXPERTISE AND TEAMs

Associate Professor Adam Wilkinson has expertise in stem cell biology and leads a research programme in ex vivo blood stem cell expansion. Associate Professor James Davies is an expert in genomics with a special interest in gene editing of inherited blood disorders.

OUR RESEARCH APPROACH

We plan to develop and optimise clinical-grade blood stem cell expansion protocols in order to generate large numbers of blood stem cells for transplantation therapies. Increasing the dose of blood stem cells available for transplantation will help more patients access this therapy and should also improve treatment efficacy and safety. We also intend to apply this approach to generate other clinically relevant mature blood cell types for transplantation and transfusion.

We also plan to develop a set of powerful tools to detect genetic mutations that may occur when modifying blood stem cells and T cells. These cells are important for a variety of medical treatments, including gene therapies, and we want to ensure they are safe and effective before being used in patients. To accomplish this, we are developing a toolkit of various techniques to assess the safety and effectiveness of manipulated cells. This will include measuring how cells are genetically modified with viruses, profiling genetic changes that occur with CRISPR editing, and using techniques to ensure that the cells are functioning correctly and not causing harm. By using various techniques, including DNA sequencing, we will determine how frequently mutations occur in the cells and where they tend to occur, which will provide insight into the safety and effectiveness of the cells.