Researchers working in the field of synthetic biology are bringing together science, engineering and computing to understand and copy the workings of biological life in new ways to achieve remarkable breakthroughs. Two studies published in Cell show how advances in this field could one day lead to cheap, reliable diagnostics for diseases like Ebola – tests that could be done rapidly in the field using only drops of blood or saliva on strips of paper embedded with synthetic biology circuits.
In the first study, the scientists, from Harvard University’s Wyss Institute for Biological Inspired Engineering in Boston, MA, describe how they brought lab-testing ability to pocket-sized slips of paper by embedding them with synthetic gene networks. They also explain how they created various diagnostics, “including glucose sensors and strain-specific Ebola virus sensors.”
Until recently, progress in synthetic biology has been hampered because scientists have only been able to develop synthetic mechanisms within living cells.
However, the study describes how the Wyss team took a giant leap by creating a system where they can design synthetic versions of biological mechanisms outside of cells.
Dr. Keith Pardee, lead author of the first paper and staff scientist at Wyss, explains:
“We’ve harnessed the genetic machinery of cells and embedded them in the fiber matrix of paper, which can then be freeze dried for storage and transport – we can now take synthetic biology out of the lab and use it anywhere to better understand our health and the environment.”
Dr. Pardee and colleagues have built a range of paper-based diagnostics and biosensors. These incorporate proteins that fluoresce and change color to show they are working.
Once freeze-dried, the paper-based tools can be stored for up to a year; they are activated by adding water.
The tools can also be used in the lab to save time and cost compared with conventional methods that use living cells and tissue.
“Where it would normally take 2 or 3 days to validate a tool inside of a living cell, this can be done using a synthetic biology paper-based platform in as little as 90 minutes,” says Dr. Pardee.
In their study, he and his colleagues describe how they tested a range of paper-based synthetic biology tools. They activated genetic switches, quickly designed and produced complex gene circuits, and programmed diagnostics that can test for antibiotic-resistant bacteria and strain-specific Ebola virus.
The Wyss team created the Ebola sensor with the help of a “toehold switch,” a new system for controlling gene expression that is very flexible and highly programmable. This is the subject of the second study.
The toehold switch was initially designed to work inside living cells, but the team managed to transfer its function to the freeze-dried paper method.
The toehold switch can be programmed to switch on the production of a specific protein after precisely detecting an RNA signature of virtually any kind. RNA signatures are sequences of genetic code that can be used to identify a broad range of infectious agents, including bacteria, viruses, yeast and parasites.
The team says it is also possible to link several toehold switches together, creating a complex circuit that can be programmed to carry out a series of steps, such as detect a pathogen and then deliver an appropriate therapy.
The video below explains how the toehold switch works:
Peng Yin, associate professor in the Department of Systems Biology at Harvard Medical School and Wyss Core Faculty Member, is senior author of the second paper. He explains that conventional synthetic biology just takes existing biological parts and rewires them to achieve a new purpose. But this complicates accuracy and functionality.
On the other hand, while the toehold switch is inspired by nature, it is entirely re-designed from scratch, he adds, noting that the study describes how they produced a device that “is a truly ‘synthetic’ gene regulator with 40-fold better ability to control gene expression than conventional regulators.”
In September 2014, Medical News Today learned how researchers are working on a way to fight drug-resistant pathogens with their own “gene-editing” system. In a paper published in Nature Biotechnology, the team describes how they used CRISPR – a gene-editing system that bacteria use to defend against attack by viruses – to target the superbugs themselves.