Engineer Your Body Functions with Programmable RNA

Illustration for article titled Engineer Your Body Functions with Programmable RNA

This week, scientists at Caltech released the first ever multi-input, "plug-and-play" synthetic RNA devices. You may have heard of Boolean logic gates in computer science, but now synthetic biologists are taking them one step further, creating organic computer programs that control the activity inside your cells. Maung Nyan Win and Christina D. Smolke have formed and tested in vivo one such system — and they say it's ready to work in mammals.In an article published with Win and Smolke's research in the October 17 issue of Science, Ehud Shapiro and Binyamin Gil describe the unique difficulties facing synthetic biologists:

The challenges of biomolecular computer engineering are best illustrated by comparing them to those of electronic computer engineering. In the latter, one can conceive of an advanced and innovative computer design, use one's favorite computer-aided design software, send the design to a chip fabrication facility, and with luck have a working electronic device in short order. In the field of biomolecular computers, one can equally dream of innovative designs that can be made, in principle, from known protein building blocks. However, protein engineering is in infancy compared to electronic circuit engineering. There is no protein design software to turn to, and no fabrication facility that can engineer a protein to a specification of its function. Therefore, researchers cannot construct their own advanced protein machinery and must make do with DNA, RNA, or naturally available proteins.


Win and Smolke made do with RNA, and the results are spectacular. Their experiment began with the determination of three main components: a sensor, an actuator, and a transmitter, each a different type of short RNA molecule. Using these three components, Win and Smolke created RNA devices that take in a molecular input and translate that to an output of a certain gene expression. In effect, these RNA devices act as internal gates within the cell. By combining these internal gates in different ways, Win and Smolke constructed logical operations within the cell that programmed for the production of certain proteins.

Illustration for article titled Engineer Your Body Functions with Programmable RNA

The result is a logical system that can take in two different inputs — theophylline and tetracycline — and produce a corresponding output — in this case, the Nobel-Prize-winning green fluorescent protein (GFP). Programmed to mimic an AND gate, the cell produces GFP only when both theophylline and tetracycline are present. Conversely, programmed as an NOR gate, the cell produces GFP only when both theophylline and tetracycline are not present. Programmed as an NAND gate, the cell produces GFP in every case but the one where theophylline and tetracycline are both present. Basic Boolean algebra meets bioengineering, and now we can order our cells around just like we do our computers. Win and Smolke's system is the first that can take in multiple inputs, which is an amazing advantage for would-be biological programmers. It's also very flexible and easy to program; scientists can treat it as a "plug-and-play" framework, in which it's easy to keep changing the components of the RNA device to allow for an infinite number of computations. And the best news is that though Win and Smolke published only the results they got from testing in yeast cells, they say that their devices will translate to mammal cells with no trouble. Your cells could soon be detecting tumors or conducting their own targeted gene therapy to fight cancer — and this at a molecular level, all under the direction of scientific and medical professionals. Sounds good to me. Caltech Engineers Build First-Ever Multi-Input "Plug-and-Play" Synthetic RNA Device [Caltech] Higher-Order Cellular Information Processing with Synthetic RNA Devices [Science] RNA Computing in a Living Cell [Science] Images from Science.


If you're going to henceforth be referring to GFP as "the Nobel-Prize-winning green fluorescent protein (GFP)", you're going to be significantly increasing your wordcount for biology-related articles: it won the Nobel Prize because it's used in approximately 90% of all genetics/synthetic biology/developmental biology research. OK, maybe only 70% of developmental biology, but 98% of synthetic biology. You get the idea.