A team of engineers at the Massachusetts Institute of Technology (MIT) has developed an exciting new system. Under the direction of assistant professor Katie Galloway, this complex system allows for custom, fine-tuned synthetic gene expression. To accomplish this, the system—called DIAL—lets researchers turn genes on at the level they want it. High, medium, low or off. This groundbreaking work has the potential to expand gene therapy applications immensely, allowing patients customized therapies for numerous ailments.
The research describing the DIAL system was released in the high impact journal Nature Biotechnology. In it, Galloway and her team show us how they were able to use promoter editing to precisely control gene expression. This inventive new paradigm has the potential to change synth bio as we know it. In particular, it offers great promise for designing therapeutics that require tight control of gene expression.
Understanding DIAL and Its Functions
DIAL is a major step forward in the control of gene expression. The benefit of defining unique set points is that DIAL gives researchers the flexibility to dial in synthetic genes to produce the right amount of activity. Such precise control is imperative in therapeutic applications, where overexpression and underexpression can both result in undesirable effects.
Galloway emphasized the versatility of the DIAL system, stating, “This is something we’re excited about because both DIAL and ComMAND are highly modular, so you could not only have a well-controlled gene therapy that’s somewhat general for a population, but you could, in theory, tailor it for any given person or any given cell type.”
The DIAL system was initially tested as researchers transformed mouse embryonic fibroblasts into motor neurons. They achieved the high expression of a particular gene that encourages conversion. This showed DIAL’s ability to produce successful, functional neurons. This dynamic process is foundational to identifying new treatments for neurodegenerative diseases, brain injuries, and other disorders which impair motor function.
The Role of Promoter Editing
That’s because promoter editing is at the heart of how DIAL works. In this approach, scientists can precisely edit the regulatory factors that govern gene expression. Galloway noted that their results indicate increased concentrations of a specific cocktail used in promoter editing enhance motor neuron production. Potentially, the most consequential finding for neuroscience research overall.
“This is an extremely powerful, stable, multifunctional tool,” Galloway said. Its modular design adapts to make it simple to control a wide range of transgenes. Tuning gene expression to exactly the right level has been for many years a semantic plasticity core challenge of synthetic biology. DIAL has come to address this challenge directly.
In addition to greater ease in creating, it is providing researchers with systems and applications that are more stable and predictable. Galloway expressed excitement regarding this achievement, stating, “We achieved uniform and stable control. This is very exciting for us because lack of uniform, stable control has been one of the things that’s been limiting our ability to build reliable systems in synthetic biology. When there are too many variables that affect your system, and then you add in normal biological variation, it’s very hard to build stable systems.”
Combining DIAL with ComMAND
Beyond DIAL’s robust standalone capabilities, DIAL can be connected to another groundbreaking system called ComMAND. This enhanced, complementary technology leverages a feedforward loop technology. This makes it a powerful tool to prevent cells from overexpressing therapeutic genes, increasing both the safety and efficacy of gene therapies.
Together, DIAL and ComMAND provide an impressive new approach to controlling gene expression. Researchers can leverage these tools to create more effective therapies tailored specifically to individual patient needs or specific cell types.
The promise of personalized medicine is increasing at a breathtaking pace. Given these considerations, this research has significant implications that extend well past motor neuron conversion alone. Turning gene expression up or down opens up thrilling new avenues for therapy. It gives us the power to treat a wide range of diseases that have a genetic component.