Recombinant Cell Surface Protein Control via Oligonucleotide Hybridization

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Solution Overview

Problem

Current systems lack the ability to easily attach, control, and reverse the attachment of proteins on cell membranes, limiting control over cellular processes and adaptability to environmental changes.

Innovation Solution

A system comprising recombinant cells expressing polypeptides with membranal anchoring and extracellular binding domains, combined with oligonucleotide-bound compounds that hybridize to attach and detach synthetic agents, allowing for dynamic modification of cell surface proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If cell surface proteins are used to mediate cellular processes, then cellular functions are achieved, but the ability to dynamically control and reverse protein attachment is limited

Engineering Contradiction:
Improvedynamic control of protein attachmentVSAvoidreversibility of protein attachment
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent introduces oligonucleotide-based intermediaries that mediate the attachment and detachment of synthetic agents to cell surface proteins. These intermediaries hybridize to the proteins, enabling controlled attachment and reversible detachment through complementary strand binding, thus providing dynamic control over protein attachment without permanently altering cellular functions

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system enables dynamic modification of cell surface proteins by allowing attachment and detachment of synthetic agents in response to environmental cues. The reversible hybridization of oligonucleotides creates a dynamic system where protein composition can be changed and reversed, transforming static cell surface structures into dynamically controllable interfaces

Inventive Principle:
Principle #15Dynamics

2Adaptability or versatility

If synthetic agents are attached to cell surfaces, then control over cellular processes is improved, but the complexity of the system increases

Engineering Contradiction:
Improvecontrol over cellular processesVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The oligonucleotide-based system provides multi-functionality by enabling attachment of various synthetic agents (fluorescent dyes, drugs, antibodies) to different cell surface proteins through a universal hybridization mechanism. This universal approach simplifies the system compared to protein-specific attachment methods while maintaining the ability to control diverse cellular processes

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system controls cellular processes by changing parameters such as oligonucleotide sequence, concentration, and hybridization conditions rather than requiring complex mechanical or structural modifications. This parameter-based control approach simplifies system operation while achieving precise control over protein attachment and cellular responses

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If cell surface proteins are modified, then adaptability to environmental changes is improved, but perturbation of cellular functions may occur

Engineering Contradiction:
Improveadaptability to environmental changesVSAvoidcellular function stability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent extracts the attachment function from the cell surface proteins themselves, using separate oligonucleotide intermediaries that bind to proteins without permanently altering them. This extraction allows synthetic agents to be attached and detached without modifying the intrinsic properties or stability of the cellular proteins, thus maintaining cellular function reliability while achieving adaptability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system enables temporary attachment of synthetic agents that can be discarded or detached when no longer needed, while the cell surface proteins remain intact and recoverable. The reversible oligonucleotide hybridization allows agents to be removed without damaging the underlying proteins, maintaining cellular function stability while providing temporary adaptability for specific experimental or therapeutic needs

Inventive Principle:
Principle #34Discarding and recovering

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 precise control over cell surface protein composition and interactions, facilitating adaptability and reversibility without perturbing cellular functions.

Implementation Method 1

a second compound comprising a second oligonucleotide (ODN-2) covalently bound to a synthetic agent, either directly or through a second linker, wherein said second oligonucleotide is complementary to said first oligonucleotide

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS20220236257A1Artificial receptors, recombinant cells comprising thereof, methods for their preparation, and method of using thereof
Publication Date: 2022.07.28 YEDA RES & DEV CO LTD
  • US20220236257A1 patent drawing
  • US20220236257A1 patent drawing
  • US20220236257A1 patent drawing

AI summary

The disclosure presented herein provides artificial receptors and a system comprising recombinant cells decorated with various labels and/or synthetic agents, wherein said labels and/or synthetic agents can be reversibly modified or removed from the cells. Also disclosed herein are methods for decorating and/or modifying the cells and methods for using thereof.