Soluble Receptor Ligands for Cell Detection
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Solution Overview
Problem
Current gene therapy strategies for correcting genetic deficiencies using retroviruses have variable outcomes and can lead to lymphoproliferative disorders, highlighting the need for more effective methods to detect and quantify membrane receptors on target cells, particularly stem cells, for precise identification and selection.
Innovation Solution
Development of soluble receptor binding ligands derived from the soluble part of enveloped virus glycoproteins, containing receptor binding domains (RBD), which interact with membrane receptors on target cells to facilitate identification, quantification, and selection of cells expressing specific receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If retroviral vectors are used for gene transfer to correct genetic deficiencies, then gene therapy can be achieved, but lymphoproliferative disorders occur and outcomes are variable
Solution Approach 1:
The patent applies preliminary action by detecting and quantifying membrane receptor expression on target cells before gene therapy treatment. This allows identification of cells with specific receptor profiles that may be prone to lymphoproliferative disorders, enabling selective avoidance or modified treatment of these cells to improve safety while maintaining therapeutic effectiveness.
Solution Approach 2:
The patent implements feedback by providing detection and quantification of membrane receptor expression as a monitoring mechanism. This feedback information can be used to adjust gene therapy protocols, select appropriate patient subsets, or modify treatment parameters to reduce the risk of lymphoproliferative disorders while maintaining therapeutic outcomes.
2Measurement precision
If membrane receptor detection methods are improved for target cell identification, then cell selection accuracy increases, but detection complexity increases
Solution Approach 1:
The patent uses soluble receptor binding ligands as intermediary molecules that bridge the detection system and membrane receptors on target cells. These ligands bind to specific membrane receptors with high affinity, enabling indirect detection through fluorescent labeling or other detection mechanisms, thereby achieving high measurement precision while simplifying the overall detection process compared to direct receptor visualization methods.
Solution Approach 2:
The patent employs fluorescent labeling of receptor binding ligands to enable detection of membrane receptors through fluorescence emission. This color-based detection mechanism provides high measurement precision through flow cytometry or fluorescence microscopy while maintaining relatively simple detection instrumentation and procedures.
3Quantity of substance
If multiple membrane receptors are detected simultaneously on target cells, then cell identification completeness improves, but detection time increases
Solution Approach 1:
The patent merges multiple detection functions into a single assay by using panel reagents that can simultaneously detect multiple membrane receptors on target cells. This combining approach allows simultaneous quantification of different receptor types (e.g., GLUT1, PiT1, PiT2) in one experiment, improving the quantity of information obtained while minimizing the time required compared to sequential detection methods.
Solution Approach 2:
The patent develops universal detection systems that can detect multiple different membrane receptors using a common platform and reagent set. This multi-functionality allows simultaneous measurement of various receptor profiles on the same target cell population, increasing detection capacity without proportionally increasing time requirements.
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 ligands enable precise identification and quantification of membrane receptors on target cells, allowing for the determination of their physiological state and selection of cells with defined receptor profiles, thereby improving the accuracy and safety of gene therapy approaches.
Implementation Method 1
The soluble receptor binding ligand is liable to interact with a membrane receptor present on the surface of a target cell
Data Source
AI summary
A method for the identification and quantification of the expression of membrane receptors present on the surface of target cells using at least two soluble receptor binding ligands derived from the soluble part of the glycoprotein of an enveloped virus that interacts with a cellular cognate receptor, the receptor binding ligand containing a part or the totality of one of the receptor binding domains (RBD) of the glycoprotein, and the soluble receptor binding ligand being liable to interact with the at least one membrane receptor of a target cell, for the identification and quantification of the expression of membrane receptors present on the surface of target cells, the identification and quantification taking place at a given time or during a given time interval, and allowing the determination of a physiological state of the target cell.