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RNA Strand Displacement for Sensing, Information Processing,
and Actuation in Mammalian Cells

Background and Motivation

In the near future, biological circuits will be much more modular and sophisticated than they are now, with a ten-fold smaller nucleotide footprint.

The Enabling Technology: Toehold-Mediated Strand Displacement

A gate strand and output strand exist as a complex that is partially bound through complementary Watson-Crick base-pairing within the S2 binding domain. The gate strand also contains an open, unbound domain called a toehold region, T*. An input strand with a free complementary toehold region, T, can bind to the toehold region on the gate strand, and subsequently displace the output strand to yield an input-gate complex. This is called a toehold-mediated strand displacement reaction. The output strand is used as an input for a downstream gate-output complex.

Background

Qian and Winfree (Science 2011) utilized DNA computation to create AND and OR logic gates in vitro. They constructed a sophisticated binary square root circuit using these gates: Each of these:

undergoes the same toehold-mediated strand displacement reaction. These reactions are fully modular and can be scaled to circuits of any degree of sophistication.

Motivation for Bringing Strand Displacement to Mammalian Synthetic Biology