Vector engineering for cellular therapies
Advances in both personalised and regenerative medicine require the stable delivery of genes to cells using a delivery system or ‘vector’. Viruses are natural vectors for DNA delivery, but the safe manufacture and delivery of DNA by virus is slow, costly, and carries inherent risk. mRNA vectors on the other hand can be made quickly, but mRNA is difficult to store and only transiently delivers genetic information to cells. DNA vectors may combine the benefits of rapid manufacture and permanent modification, together with enhanced stability.
As part of the FI EMS we are engineering new ways to deliver DNA to patient cells using vectors made almost entirely out of Human DNA sequences. We aim to decrease manufacturing cost and time, while increasing safety, helping bring personalised medicine into the clinic.
To do this we are using high-throughput DNA synthesis to build libraries of tens of thousands of DNA modules, which can be assembled together to form DNA vectors much like LegoTM bricks. We then study the behaviour of thousands of vectors in millions of cells using next generation DNA sequencing. We analyse the results using machine learning to gain an understanding of what makes a successful vector, and then iterate this process to create even better vectors.
The image below shows bacteria transformed with various coloured chromophore modules to illustrate the functionality of our modular cloning system.
Project Lead