Researchers at Caltech have taken an interesting approach to synthetic biology. They’ve engineered a Lego-like toolkit of peptides that can be put together in different ways to initiate various cellular functions. In their new proof-of-principle work, a team of researchers in the lab of Michael Elowitz, Howard Hughes Medical Investigator, created a circuit that can detect whether a cancer-causing gene is active in cells that it’s added to. If the circuit senses that the cancer gene is turned on, it causes the cells to self-destruct. This work has been reported in Science.
A cornerstone of biological research is the modification of cellular function, which has often been achieved by modifying the genome. Synthetic biology also employs gene editing to confer new abilities in the cell, like the detection of disease. Elowitz noted, however, that one goal of synthetic biology is to use less permanent tools; genome edits are often passed on to a new generation.
Therapeutic ‘circuits’ that can be controlled or removed is one way to achieve that goal. Such as circuit could be administered, which would stimulate some targeted, specific process, and then wash out or get deactivated when no longer needed. Instead of hitting on many cells randomly, it might be used only on cells where it's found that something's gone awry.
"One of the biggest challenges in biomedicine is specificity: How do you make a therapeutic that will affect only a particular type of cell? Then, how do you respond by modifying that cell in a very specific way?" explained Elowitz, who is a professor of biology and biological engineering. "These tasks are challenging for drugs, but biological circuits could excel at them. Protein circuits can be programmed to sense many types of information, process it, and respond in different ways. In fact, the reason our cells usually work as well as they do is the incredible power of our natural biological circuitry."
Just like transistors get wired together in a variety of ways to make electronic circuits, this new toolkit can generate different circuits from protein building blocks. Led by Xiaojing Gao, postdoctoral fellow, and Lucy Chong, graduate candidate, the researchers suggested that the toolkit will be used to assemble systems that can sense and respond to cellular conditions.
The team started out with a circuit that can detect an active cancer gene and if it finds it, initiate destruction of the cell. That circuit is harmless when applied to normal cells. There is a lot of potential for this technology, however. "This work is simply a proof of principle, and we haven't demonstrated these functions in animals yet," Gao noted. "However, this framework could help us transition to using programmable, cell-based therapies as medicines."
"A lot of work has been done on protein engineering, but this is the first time that we have engineered proteins that regulate—or interact with—one another in similar ways, which allows them to be combined as useful building blocks," Chong added.