RNA-Based Logic Circuits with RNA-Binding Proteins

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Solution Overview

Problem

Current synthetic biology approaches rely exclusively on transcriptional regulation, lacking control mechanisms for replicon-based expression, and existing post-transcriptional devices exhibit low dynamic range, making them unsuitable for scalable genetic circuit construction.

Innovation Solution

Development of synthetic RNA circuits that utilize RNA-binding proteins and microRNAs to regulate protein production post-transcriptionally, allowing for complex circuit construction and specific expression control by encoding proteins that bind to RNA motifs and inhibit production, with optional small molecule regulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If transcriptional regulation is used for genetic circuit design, then control mechanisms are established, but control over replicon-based expression is lacking

Engineering Contradiction:

Improvecontrol mechanismsVSAvoidcircuit construction

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent introduces RNA-binding proteins as intermediary molecules that bridge transcriptional and post-transcriptional regulation. These proteins bind to specific RNA motifs to control gene expression at the post-transcriptional level, providing the missing control mechanism for replicon-based expression while maintaining circuit modularity

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs microRNAs that recognize specific sequences in target mRNAs to regulate protein production. By changing the regulatory parameter from transcriptional to post-transcriptional control, the system achieves versatile control over replicon-based expression without increasing overall circuit complexity

Inventive Principle:

Principle #35Parameter changes

2Productivity

If existing post-transcriptional devices are used, then protein production can be regulated, but dynamic range is very low

Engineering Contradiction:

Improveprotein production regulationVSAvoiddynamic range

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent creates dynamic control systems using RNA-binding proteins that can be induced or repressed by small molecules. This allows the system to switch between different expression states with high dynamic range, overcoming the static nature of existing post-transcriptional devices

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent implements feedback mechanisms where RNA-binding proteins regulate their own expression or the expression of other circuit components. This feedback control enables precise tuning of protein production levels and expands the dynamic range of the system

Inventive Principle:

Principle #23Feedback

3Productivity

If existing post-transcriptional devices are used, then some regulation is achieved, but devices are not suitable for construction of scalable circuits

Engineering Contradiction:

Improveregulation capabilityVSAvoidscalability

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent divides the genetic circuit into modular segments: RNA-binding protein encoding sequences, RNA motif sequences, and output sequences. Each module can be independently designed and assembled, enabling scalable circuit construction while maintaining regulation capability

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates universal RNA-binding protein modules that can recognize multiple different RNA motifs. This multi-functionality allows the same regulatory protein to control multiple target genes, facilitating the construction of scalable and adaptable genetic circuits

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables sophisticated output control and scalable circuit construction with improved dynamic range, allowing for therapeutic protein expression and immune response induction while avoiding genomic integration risks.

Implementation Method 1

the at least one first microRNA represses translation of or degrades the sequence encoding the protein that specifically binds to a RNA motif and inhibits protein production

Methodology Applied

Scientific EffectRNA interference: