[marktangotango]

Two reasons I can think of; biochemical reaction pathways can be tremendously complex with subtle feedback mechanisms that are non obvious, secondly, DNA encodes mRNA that encodes proteins; determining protein folding from the sequence of DNA is exceeding difficult, so, just because you can 'write DNA programs' doesn't mean you can actually do anything with the result. Both of these factors taken together mean, that with current technology, it's really hard problem to modify DNA, to influence existing biochemical processes, or create new biochemical processes. I studied molecular biology in the 90's so I'm a bit out of date, but I believe this is still the state of affairs.

[abecedarius]

Engineering new circuits isn't the same kind of problem as understanding natural ones, just as designing a protein to fold predictably came many years ahead of predicting the folding of natural proteins. (The former started in the 80s, and the latter is afaik still very hard, as you say.) http://www.dna.caltech.edu/courses/cs191/index.html gets into some of the recent progress (under "Nucleic acid circuits").

That said, it's not my field and I get the impression they're talking more about in vitro work on the page I linked. Even if your circuits work all the time in the lab, in a cell I'd expect all kinds of things to mess with them.

[jamessb]

'Nucleic acid circuits'/'DNA circuits' are conceptually entirely different to 'genetic circuits'.

In the former, you design sequences of DNA such that complementary base pairing means they can displace each other in cleaver ways. This lets you create some interesting things, like oscillators [1], amongst others [2]. These do not need any of the apparatus of the cell to function, so work in solution; indeed, if they were inside cells they would get digested by nucleases. The thermodynamics of DNA/RNA folding is fairly well understood, and the range of structures in much more limited than that of proteins. A major drawback of these circuits is that they function very slowly.

By 'genetic circuits', people usually mean a genetic regulatory network [3] - essentially you combine existing genes in new ways, by chaing the regulatory sequences before each gene. For example, you can construct an oscillator from three genes by having the first repress the second, which represses the third, which represses the first [4]. Here you aren't designing new proteins (which is extremely hard), but rather modifying existing ones. Since these circuits require producing new proteins from DNA, they require RNA polymerase, the proteosome, ATP, the necessary monomers etc. so can only function inside a cell (or cell-free expression system containing these components).

[1]: https://www.researchgate.net/publication/50304896_Programmin...

[2]: http://research.microsoft.com/en-us/projects/dna/

[3]: https://en.wikipedia.org/wiki/Gene_regulatory_network

[4]: https://en.wikipedia.org/wiki/Repressilator