RNA Control Devices for Protein-Responsive Gene Regulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current engineering of gene networks is limited by the inability to effectively interface with native components, lacking alternative platforms for widespread applications in research, biotechnology, and medicine.
Innovation Solution
Development of RNA control devices that utilize alternative splicing to couple protein abundance to targeted gene expression events, enabling programmable sensing-actuation devices to detect signaling pathways and rewire cellular behaviors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If engineered gene networks are attempted using conventional methods, then some level of gene network engineering can be achieved, but the ability to interface with native components is limited
Solution Approach 1:
The patent introduces RNA molecules as intermediary components that bridge engineered control elements and native cellular machinery. The RNA molecules contain aptamer domains that bind to specific proteins and regulatory sequences that interact with native transcription factors and splicing machinery, enabling engineered networks to interface with native components without direct protein-protein interactions.
Solution Approach 2:
The patent replaces conventional protein-based gene regulation mechanisms with RNA-based regulation. Instead of using engineered proteins to bind DNA and regulate transcription, the system uses RNA molecules that can be transcribed by native polymerases and processed by native splicing and translation machinery, substituting a more compatible biological mechanism.
2Extent of automation
If RNA control devices utilize alternative splicing to couple protein abundance to targeted gene expression, then programmable sensing-actuation can be achieved, but the complexity of the RNA device structure increases
Solution Approach 1:
The RNA device is segmented into distinct functional domains: an aptamer domain for protein binding, a regulatory sequence domain for splicing control, and a coding sequence domain for gene expression. This segmentation allows each component to perform its specific function independently while maintaining overall device functionality through their coordinated arrangement.
Solution Approach 2:
The RNA device incorporates dynamic alternative splicing that responds to protein binding events. The splicing pattern dynamically changes based on the presence and concentration of target proteins, allowing the device to automatically sense and respond to cellular conditions without external intervention.
3Reliability
If aptamers are integrated near regulatory sequences for alternative splicing, then protein binding can modulate splicing patterns and gene expression, but the precision of controlling alternative splicing may be affected
Solution Approach 1:
The patent places aptamers at specific local positions within intronic regions near alternative splicing regulatory sequences. This local integration allows the aptamer to specifically influence the splicing decision at nearby exon-intron boundaries while maintaining the overall splicing pattern of other exons, providing precise spatial control over the modulation effect.
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
These RNA devices allow for autonomous control over cellular behavior, linking disease markers to noninvasive sensing and reprogrammed cellular fates, enhancing our ability to modulate gene expression in response to cellular signals.
Implementation Method 1
an aptamer that binds a protein ligand; binding of the protein ligand to the aptamer enhances or inhibits the function of the regulatory sequence
Implementation Method 2
a sequence capable of undergoing alternative splicing; binding of the protein ligand to the aptamer enhances or inhibits the function of the regulatory sequence to alter alternative splicing pattern and expression of the coding sequence
Data Source
AI summary
The invention described herein relates to an RNA-based control device that senses the presence and/or concentration of at least one protein ligand, preferably through its protein-binding aptamer domain, and regulates a target gene expression through alternative splicing of the target gene in which the RNA-based control device is integrated. The device has uses in therapeutic as well as diagnostic applications.