How we work in real world.
Our project presented PREDATOR Pro, a novel targeted protein degradation system directly regulated by exogenous signals. PREDATOR Pro is highly modularized, with replaceable features to easily change the targeting module that interacts with the target protein, and the interface where the signal responsive feature can be altered. As a foundational advance project, our project can potentially be used in wide range of scenarios. Here we list three possible real-world implementations of our design and discussed the possible safety issues and challanges we may have to address.
Possible working scenarios, concerns and challenges
1. In our opinion, the end users of iGEM 2020 project would mainly be scientists working on synthetic biology. PREDATOR Pro is a new regulatory tools with which protein abundance can be directly controlled by signal-responsive protein dimerization, providing possibilities for acute response on rapidly changing signals including cellular signaling pathways since (MAPK pathway, ATK pathway etc.) phosphorylation triggered protein dimerization has been widely reported in these pathways. Minimum safety and ethical concerns are raised under such scenario.
2. For scientists working on gene function researches, PREDATOR Pro can also provide solution on developing cellular or animal model to knockdown the expression of specific gene under given stimulus. Such approach could be especially useful for genes that are lethal under knockout conditions. With light controlled or thermal controlled PREDATOR Pro system, highly precise tissue specific knock down can be achieved. In this scenario, further optimization should be conducted on the PREDATOR Pro system to reduce the leakiness caused by the background dimerization. Affection of constitutive or tissue specific PREDATOR Pro overexpression in animals should also be evaluated.
3. There is also some possibility that our project might be used for therapeutic purposes. It has been reported that aggregation of specific proteins was related to multiple diseases. In this case, PREDATOR Pro can be used to control the target protein abundance within physical level, thus maintaining the original function of such protein. In this case, the delivery and expression of PREDATOR Pro system would raise safety concerns especially regarding the specificity of the delivery. Also, huge amount of optimization and trial experiments should have been conducted before the application is pushed this far.
As a methodology study in an exceedingly early stage, we do understand that there will still be countless challenges and setbacks waiting ahead of us. But we do believe that with efforts and love, our project may help making a better world somehow :-)