So much of science is patience. A research advance from a team led by Christina Smolke—engineering molecules to perform sophisticated functions in cells—has provoked enthusiasm well beyond Stanford and now will continue down the road to full development for, oh, a minimum of eight years.
That's how long assistant professor of bioengineering Smolke estimates it will take to see the impact of her innovation on human health. The achievement so far is the construction of biological molecules that can enter a cell, recognize what's occurring within it and respond accordingly. Eventually those molecules could have enormous therapeutic value, such as the ability to detect disease and attack it with a precision that avoids undesired consequences, such as damage to healthy cells. Consider, for example, the possibility of using engineered molecules to identify cancerous cells and then induce those cells to destroy themselves.
In Smolke's field, this type of accomplishment generates immediate excitement despite the long road ahead. James Collins, a Boston University professor of biomedical engineering and 2003 recipient of a MacArthur Foundation "genius" award, says the work "represents an important breakthrough in synthetic biology."
"This innovative development," Collins wrote in an email to STANFORD , "enables us to easily rewire and reprogram mammalian cells, as well as create novel classes of biosensors that can be used to detect and monitor disease states." Smolke's lab, he continued, has "moved the field much closer to clinical applications." Working closely with Smolke were Caltech researchers Stephanie Culler, first author on a paper about the results in Science, and Kevin Hoff.
The jump-off point for Smolke's team is the process of creating molecules of RNA (ribonucleic acid, which is genetic material) that can be designed as control devices to biologically compute what cells are doing, then transmit a programmed response. The researchers succeeded in using that kind of synthetic device to sense conditions in cultured human cells.
Illustration: Yarek Waszul
"We're demonstrating that you can encode this type of sophisticated function in RNA molecules," says Smolke. "But there are still a lot of steps to go through that are not trivial to get to clinical trials. This is pretty new stuff. This is the first time these types of molecules are being designed this way."
The engineered RNA devices also have a particularly pragmatic elegance: Their modular design allows their components to be interchanged. For instance, one piece could be varied as needed to make cells receptive to one drug versus another, depending on which would be more therapeutic. "We really focus on the technology involved and the modular aspect," Smolke notes. "We're developing something that can be tailored for specific results."
The next major research stage is animal studies. "That's where we begin figuring out how this actually works in whole organisms," Smolke says. Collaborative efforts also are under way with Michael Jensen, a clinician at Seattle Children's Research Institute, on the lengthy path of translating the research to a human clinical trial.
Smolke's work on designer RNA molecules began when she was an assistant professor of chemical engineering at Caltech. Working there with Maung Nyan Win, then a graduate researcher and later a Stanford postdoc, Smolke's efforts produced the first RNA device that could detect and process more than one piece of incoming information after entering cells. Smolke joined Stanford's faculty in January 2009.
"It has taken an incredibly talented and dedicated team to get the technology to where it is today," Smolke says. "We have a long road ahead of us in translating these technologies into human patients. But the promise and potential for treating many devastating diseases make the journey . . . exciting and worthwhile."
