Engineered TRS Motifs for Targeted Protein Binding

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Solution Overview

Problem

Current methods for harnessing biological diversity are limited in variability and do not fully exploit the structural and functional diversity found in nature, restricting the repertoire of tools and techniques for targeting and modifying biological systems.

Innovation Solution

Engineered proteins or polypeptides comprising Photorhabdus target recognition sequences (TRS) motifs, which are designed to bind to specific targets, are developed. These TRS motifs are flanked by hydrophobic and charged regions and can be optimized for expression in various host cells, allowing for targeted binding or modification of substrates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current methods for harnessing biological diversity are used, then the process is simple and familiar, but the variability and repertoire of tools are limited

Engineering Contradiction:
ImprovevariabilityVSAvoidcomplexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The invention segments biological diversity into discrete, modular target recognition sequences (TRS) that can be independently identified, characterized, and applied. By breaking down complex biological systems into reusable sequence modules, the invention enables systematic exploitation of variability while maintaining manageable complexity through standardized assembly procedures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the parameter of biological variability by systematically identifying and characterizing multiple TRS sequences with different specificities and affinities. This allows selection and application of appropriate sequences for different targeting needs, expanding the repertoire of tools without requiring complete redesign of the underlying methodology.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If engineered proteins with TRS motifs are developed, then targeting specificity is enhanced, but the complexity of protein engineering increases

Engineering Contradiction:
ImprovespecificityVSAvoidengineering complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention performs preliminary action by pre-identifying and characterizing TRS sequences from Photorhabdus proteins before application. These pre-characterized sequences serve as ready-to-use modules that can be directly incorporated into engineered proteins, eliminating the need for de novo design and reducing engineering complexity while maintaining high specificity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention uses copying by replicating and applying identified TRS sequences across multiple engineered protein constructs. Once a TRS sequence is characterized for binding to a specific target, it can be copied and used in various protein contexts, achieving consistent high specificity without repeating the entire characterization process.

Inventive Principle:
Principle #26Copying

3Adaptability or versatility

If TRS motifs are engineered for binding to specific targets, then the repertoire of targeting tools is expanded, but the difficulty of identifying and characterizing new sequences increases

Engineering Contradiction:
ImproverepertoireVSAvoididentification difficulty
Core Design Contradiction:
Adaptability or versatilityVSDifficulty of detecting and measuring

Solution Approach 1:

The invention applies universality by developing a standardized methodology for identifying and characterizing TRS sequences that can be applied across different Photorhabdus proteins and target types. This universal approach allows systematic expansion of the repertoire while managing identification difficulty through consistent procedural frameworks and shared knowledge bases.

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

The engineered proteins or polypeptides with TRS motifs provide enhanced specificity and versatility in targeting and modifying biological systems, enabling increased or decreased expression of target molecules and substrates, thus expanding the capabilities for therapeutic and diagnostic applications.

Implementation Method 1

engineered proteins or polypeptides comprising one or more engineered Photorhabdus target recognition sequence (TRS) motifs... which are designed to bind to specific targets

Methodology Applied
Scientific EffectProtein-protein binding:

Data Source

PatentUS11999767B2Target recognition motifs and uses thereof
Publication Date: 2024.06.04 THE BROAD INST INC
  • US11999767B2 patent drawing
  • US11999767B2 patent drawing
  • US11999767B2 patent drawing

AI summary

The disclosure provides novel programmable targeting sequences and applications thereof. The targeting sequences can be engineered for binding to proteins, polypeptides, and other macromolecules.