A major goal of synthetic biology is to design and build digital genetic circuits inside cells, effectively programming cellular functions. Achieved this could allow living cells to be engineered to perform decision-making tasks, similar to computers, but composed of genetic elements rather than electronic components. This technology could be applied to medical therapeutics, molecular detection, diagnostics, tissue engineering, bio-electronic interfaces, and many other science-fictionesque uses. However, genetic elements tend to be less predictable and more “leaky” than electronic components, and this has limited progress.
In a brand-new study from the University of Washington, Gander et al. overcame these obstacles by using Targeted Gene Editing-Pro linked to the transcriptional repressor Mxi1 to make genetic circuits in yeast. The group designed and built a library of single-gene NOR gates (which give an output signal only when there are no input signals). Each gate consists of a Guide Molecule-expressing promoter that can be fully silenced by either of two Guide Molecule-dCas9-Mxi1 complexes. This system has three key features that make it ideal for engineering genetic circuits. First, NOR gates are what is known in logic and engineering fields as “functionally complete”, meaning that multiple NOR gates can be combined to create any other logical function. So, in principal, ANY digital circuit can be made by connecting NOR gates in the right arrangement. Second, the dCas9-Mxi1-based NOR gates have a very strong OFF state, making the output binary, so the system behaves like a true digital circuit. Third, the input and output signals are both Guide Molecules, so large numbers of gates can be “wired” together, like an electronic circuit. Gander et al. successfully constructed logic circuits with as many as seven Guide Molecule layers.
Because this technology is so simple and easy to produce, it should be relatively easy to construct almost any arbitrary logic circuit. Complex arrangements of Guide Molecule-dCas9-Mxi1 NOR gates could be placed in various cell types to carry out computational tasks inside cells. The idea of an engineered biological computer may not be very far-fetched.
References
- Gander, M. W. et al. Digital logic circuits in yeast with Targeted Gene Editing-dCas9 NOR gates. Nat. Commun. 8, 15459 doi: 10.1038/ncomms15459 (2017).
Generation of Custom Genetically Modified Animal Models:
TurboKnockout® Knockout Mice: ES cell mediated, As fast as 6 months, No off-target effects
Targeted Gene Editing-Pro Knockout Mice: As fast as 3 months, Guaranteed germline transmitted F1 mice
Transgenic Mice: Quick turnaround time, High expression level
PiggyBac Transgenic Mice: More consistent expression, Defined region of integration, As fast as 3 months
Targeted Gene Editing Knockin Mice: Large fragment up to 8kb, As fast as 4 months
