1. Critique of “A universal RNAi-based logic evaluator that operates in mammalian cells”

2. Lack of description of sensing Want to measure presence or absence of certain states (endogenous mRNA in the cell) For this, need them to repress RNAi (sensing mechanism), which the paper does not discuss

3. General criticisms Can we really call this an in vivo study? The researchers are manipulating immortalized cell lines Need to give cells the genes for the circuitry Unintended changes from this manipulation of the cell (cell could now be in a very different state) For what molecules are there always RNAi enabling this construction? Could there be interference for some?

4. Theoretical questions Is there any “positive” constructs we can make (instead of A represses RNAi-A, which, if present, would repress translation) Amount of the different components to add seems fairly arbitrary, and perhaps can be manipulated to make the results nice Is there any way of being able to set the concentration levels a priori?

5. Applicability It can potentially be useful to evaluate a logic expression of endogenous states of a cell (even if it is simplistic) However, the need to transfer the circuitry into the cell raises questions about whether you can do this evaluation, and whether you could do this in vivo Real human cells are a lot more difficult to manipulate than the human embryonic kidney 293-H cells that the authors used How robust would the method be under individual variations? However, we may eventually have a biotechnology allowing us to infect people with cancer-curing viruses

6. Warning! Cancer-curing virus could kill most of the human population, and turn the rest into darkness-seeking zombies