Unique Regulatory Element Strength Identification via Barcode Segmentation

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The relationship between nucleic acid sequences and the function of regulatory elements, such as cis-regulatory elements and trans-regulatory elements, remains poorly understood, limiting efficient approaches for controlling gene expression in fields like synthetic biology and medical genetics.

Innovation Solution

A method involving synthetic nucleic acids with unique regulatory elements and barcodes is used to identify the strength and conformational effects on transcribable reporter sequences by expressing them in cells and determining the expression frequency of barcodes, allowing for the assessment of conformational changes and regulatory element strength.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If synthetic nucleic acid sequences with unique regulatory elements are expressed in cells to identify regulatory element strength, then measurement precision of regulatory element function is improved, but device complexity and experimental setup complexity increases

Engineering Contradiction:

Improveregulatory element strength identificationVSAvoidexperimental setup complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The regulatory element is segmented and paired with a unique barcode sequence, allowing individual identification and measurement of each regulatory element's strength independently within the complex synthetic nucleic acid sequence

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The barcode sequence acts as an intermediary marker that links the regulatory element to detectable signals, enabling precise measurement of regulatory element function without directly measuring the complex nucleic acid structure

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If conformational changes in nucleic acid sequences are introduced to study regulatory element function, then measurement precision of conformational effects is improved, but difficulty of detecting and measuring increases

Engineering Contradiction:

Improveconformational effect detectionVSAvoidconformational change detection

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses barcode sequences as detectable markers that change or vary based on conformational states, enabling precise detection and measurement of conformational effects through barcode analysis rather than direct structural measurement

Inventive Principle:

Principle #32Color changes

3Productivity

If multiple synthetic nucleic acid sequences with different regulatory elements are expressed simultaneously, then productivity of regulatory element screening is improved, but loss of information about individual element contributions increases

Engineering Contradiction:

Improveregulatory element screening efficiencyVSAvoidindividual element contribution data

Core Design Contradiction:

ProductivityVSLoss of information

Solution Approach 1:

Each regulatory element is assigned a unique barcode sequence, segmenting the information so that individual element contributions can be tracked and identified even when multiple elements are expressed simultaneously in the same cell population

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The barcode sequences provide feedback information about which regulatory elements are active and their relative strengths, enabling the system to distinguish individual element contributions through barcode frequency analysis in the expressed sequences

Inventive Principle:

Principle #23Feedback

Data Source

PatentUS20230037026A1Method for identifying regulatory elements conformationally

Publication Date: 2023.02.02 ASKBIO INC

AI summary

The present invention provides a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence.