Improving the safety of the TDP-REG technology for gene therapies for MND.
Principal Investigator: Dr Oscar Wilkins
Lead Institution: University College London
MND Association Funding: £329,915*
Funding dates: February 2025 - January 2028
*Supported by the Lady Edith Wolfson Fellowship Programme
About the project
The nuclear protein, TDP-43, prevents unnecessary pieces of genetic material, called cryptic exons, from being mistakenly included in the final instructions (mRNA) that the cell uses to make proteins. In most cases of MND, however, TDP-43 moves out of the nucleus and accumulates in the cytoplasm of nerve cells, allowing defective mRNA instructions to be made in the nucleus. Oscar has previously developed a method, called TDP-REG, that uses this faulty system to sneak into the cell and activate potentially therapeutic genetic fragments that are hidden in cryptic exons. The elegance of this method is that the therapies are only activated in diseased cells, which reduces the risk of side effects, creating new treatment options for MND that might otherwise be too risky. This project will use AI along with cell and animal models of MND to improve the safety of the TDP-REG technology and reduce the risk of off-target activation in healthy cells.
What could this mean for MND research?
This project will enable gene therapies to be delivered more safely to people with MND. Ultimately this research will produce highly validated methods for the delivery of gene therapies, that can be used by MND researchers worldwide.
Resources
Project code: 2426-799
