Compact RNA sensors for increasingly complex functions of multiple inputs

Area of Science:

• Molecular Biology
• Synthetic Biology
• Computational Biology

Background:

• Designing single molecules for complex computations remains a significant challenge in molecular design.
• Existing methods often lack the precision and versatility required for sophisticated molecular sensing.

Purpose of the Study:

• To demonstrate high-throughput, iterative experimental testing of diverse RNA designs for complex molecular functions.
• To develop compact, single-molecule sensors for various applications, including disease diagnostics.

Main Methods:

• Crowdsourcing diverse RNA designs from the online game Eterna for high-throughput experimental testing.
• Iterative design and testing to create RNA sensors with increasingly complex functions.
• Developing the Nucleologic algorithm for designing compact RNA and DNA sensors.

Main Results:

• Successfully designed single-input RNA sensors with high activation ratios.
• Created logic gates (XOR, XNOR) and sensors responding to the ratio of two inputs.
• Developed 85-nucleotide sensors for diagnosing active tuberculosis based on gene segment ratios.

Conclusions:

• High-throughput experimental testing of crowdsourced designs enables complex molecular computation.
• Compact, single-molecule sensors can be designed for sophisticated functions, expanding applications in diagnostics and beyond.