Background

Synthetic biology is the discipline of engineering application-driven biological functionalities that were not evolved by nature. Early breakthroughs of cell engineering, which were based on ectopic (over)expression of single sets of transgenes, have already had a revolutionary impact on the biotechnology industry, regenerative medicine and blood transfusion therapies.

Now, we require larger- scale, rationally assembled genetic circuits engineered to program and control various human cell functions with high spatiotemporal precision in order to solve more complex problems in applied life sciences, biomedicine and environmental sciences.

This will open new possibilities for employing synthetic biology to advance personalized medicine by converting cells into living therapeutics to combat hitherto intractable diseases.

A major challenge in the field of synthetic biology is: How to confine the expression of any gene of interest only to pre-selected cells. Some solutions tackle this problem by requiring simultaneous activation of two different promotors, however even such solutions inevitably allow basal expression of the gene of interest when only one of the two promoters is active.

Our Innovation

This invention provides a solution to this challenge through a new genetic platform which guarantees zero expression of the gene when only one of the two promotors is active, thus paving the way for multiple clinical applications of markedly increased safety.

Application for use:

One example for potential application is an immunomodulatory gene circuit platform hat enables tumor-specific expression of immuno-stimulators that permits selective T cell-mediated killing of cancer cells, but not of normal cells, is developed. This platform shows prolonged survival in a mouse cancer model and has the potential to be adapted to express a range of other immune regulators and to treat other cancer types.

Highlights  

  • Synthetic RNA-based circuits enable tumor-specific immune-modulator expression
  • These circuits trigger tumor-specific killing by T cells in vitro
  • Circuit-mediated immunomodulation enacts effective antitumor responses in vivo
  • This approach can be adapted to target multiple cancer types