For synthetic biologists, DNA and RNA sequences are receivers, senders, reporters, and actuators. These bioblocks make devices, and devices are connected to make systems. Parts, devices, and systems can be combined in self-contained modular units.
The BioBricks Foundation maintains the shared repository of standardized biological parts that can be assembled in a standardized way. Thus created, synthetic biological systems can be used for the purposes of capturing and processing the information, producing energy or manufacturing biomaterials.
The emerging field of functional RNA engineering offers considerable advantages over the engineering of more common protein-based devices, as RNA-based devices are nonimmunogenic and more readily programmed. Its versatile sensing and actuation functions make RNA a powerful design substrate in synthetic biology.
Christina D. Smolke, Ph.D., department of bioengineering, Stanford University, has designed RNA devices that sense increases in target protein signals that trigger certain cellular behaviors, such as the uncontrolled cell growth associated with cancer. Next, sensing of disease-related signaling by the RNA devices can be coupled to new cellular behaviors, such as cellular apoptosis.
“We envision that our devices will be delivered via viral vectors or nanoparticles to cells and can actuate responses specifically in diseased cells based on molecular markers of disease. Another application of these genetic devices is modification of stem cells and immune cells to improve their therapeutic potential. Our RNA devices can regulate various cellular functions, including proliferation and therapeutic efficacy.”
Dr. Smolke’s RNA device is a synthetic gene with built-in sequences for RNA aptamers. Aptamers are short noncoding RNAs that are able to recognize specific ligands such as proteins; essentially acting as the RNA analog of antibodies.
When the gene module is transcribed into RNA, the RNA aptamers bind to the target proteins. This binding event in turn hinders or disrupts a potential splicing event, resulting in the binary regulation of the RNA splicing event (spliced/not-spliced), which can be coupled to any type of genetic output, like a fluorescent signal or an apoptotic event.
The device’s specificity is enhanced by incorporating additional aptamer sensors against other signaling proteins. “Both the input processing function and genetic output are modular and can be altered to suit multiple applications,” says Dr. Smolke. “One can extend these systems to create quite sophisticated RNA-processing devices that are able to differentiate signals from complex regulatory networks.”