Heterochiral translators for nuclease-resistant DNA computing

This technology is a heterochiral DNA logic circuit that converts D‑DNA/RNA inputs to stable L‑DNA outputs via strand displacement, enabling nuclease‑resistant, bio-orthogonal sensing of natural signals.

Unmet Need: Molecular circuits stable to nuclease degradation

DNA strand displacement currently serves as a powerful chemical framework for implementing enzyme-free molecular circuits. Previous studies have demonstrated its potential for intracellular biomarker sensing and for enabling diagnostic or therapeutic decision-making in vivo. However, a major obstacle to the application of these systems in cellular environments is the susceptibility of circuit components to nuclease-mediated degradation. Accordingly, there is a need for molecular circuit designs that maintain stability and resist degradation within cells.

The Technology: Heterochiral DNA logic circuits

This technology uses DNA-style logic circuits that take an input strand of one chirality (e.g., D-DNA) and, via two translator complexes, generate an output strand of the opposite chirality (e.g., L-DNA) via strand-displacement reactions. This heterochiral design makes the circuits resistant to endogenous D-nucleases and largely invisible to native nucleic-acid processes, while still allowing them to respond to natural D-DNA or RNA inputs.

This technology has been validated in vitro using a multistep leakless translator architecture.

Applications:

  • Intracellular biosensors
  • Therapeutic aptamers
  • Protected DNA nanostructures
  • Smart drug-delivery nanocarriers
  • Molecular computing and logic devices

Advantages:

  • Superior nuclease resistance
  • Reduced leak and higher signal fidelity
  • True biorthogonality
  • Predictable stereochemical control
  • Seamless D/RNA input compatibility

Lead Inventor:

Milan Stojanovic, Ph.D.

Patent Information:

Patent Issued (US 12,529,103)

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