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Synthetic Gene Circuits With Improved Safety

Nissim Lior , HUJI, School of Medicine - IMRIC

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. 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.

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