ProjectsA platform for engineering cell-type specific vectors for personalised medicine

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. 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: decreasing costs and manufacturing time, while increasing safety.

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 a candidate vector in a semi-random fashion - much like LegoTM bricks. We then study the behaviour of the thousands of assembled vectors in millions of cells using next generation sequencing of barcodes encoded in the vector DNA, and analyse the results using machine learning to gain an understanding of what makes a successful vector. We then iterate this process to create even better vectors – and the scalable and reusable nature of our platform enables us to repeat the process in different cell types, allowing us to create vectors specifically tailed to a particular tissue.

This cross disciplinary work integrates biologists’ synthetic biology and next generation sequencing expertise with machine learning and engineering expertise from computer scientists. The FI-EMS is supporting this project by funding the construction of even larger libraries of modules, and making available a new DNA sequencing device from GenapSys that allows FI-EMS members to sequence DNA libraries more quickly and at a lower cost than before in their own labs, speeding the iterative cycle of ‘build-test-learn’ underpinning this work.

Personalised Medicine

Project Lead

Prof. Dr. Michael Platten
Department of Neurology, Medical Faculty Mannheim, MCTN & DKFZ