Viral-Binding Protein Reagents for Viral Purification and Cell Transduction
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Solution Overview
Problem
Existing methods for generating cell populations for cell therapy, such as those involving genetically engineered immune cells like T cells, are inefficient and require improved techniques for viral particle purification and cell transduction.
Innovation Solution
Development of proteins comprising a viral-binding domain and a streptavidin-binding partner, often with heparin-binding domains, which can be used for purifying viral particles and transducing cells, including methods for on-column transduction using chromatography columns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used for viral particle purification and cell transduction, then the processes are simpler to perform, but the efficiency and productivity are low
Solution Approach 1:
The patent employs heparin-binding domains as intermediary molecules that mediate the interaction between viral particles and chromatography resin. The heparin-binding domain acts as a bridge, allowing viral particles to be captured on the chromatography column through heparin-viral interactions, while the streptavidin-binding partner enables specific attachment to biotinylated resin. This intermediary mechanism significantly improves purification efficiency without requiring direct complex modifications to the viral particles themselves.
Solution Approach 2:
The invention creates a composite protein structure combining heparin-binding domains (for viral particle recognition and binding) with streptavidin-binding partners (for immobilization on biotinylated resin). This composite approach allows the system to simultaneously achieve specific viral binding and stable chromatography column attachment, resolving the contradiction between simplicity and efficiency by integrating multiple functions into a single reagent.
2Productivity
If conventional cell transduction methods are used, then the procedure is straightforward, but the transduction efficiency is insufficient for effective cell therapy
Solution Approach 1:
The patent implements preliminary action by first capturing viral particles on the chromatography column using heparin-binding domains before introducing target cells. This pre-concentration and pre-positioning of viral particles on the column creates an optimized transduction environment, ensuring high local viral concentration at the site of cell contact. The streptavidin-binding partner is also pre-attached to the biotinylated resin, establishing the complete system before the actual transduction event occurs.
Solution Approach 2:
The invention replaces conventional mechanical mixing and incubation methods with a chromatography-based system where viral particles are immobilized on the column and cells pass through under controlled flow conditions. This substitution of mechanical transduction methods with a chromatography-based approach enables more efficient viral-cell contact while maintaining operational simplicity through standardized chromatography procedures.
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
Enhances the efficiency of viral particle purification and cell transduction processes, providing improved methods for generating cell populations suitable for cell therapy.
Implementation Method 1
the viral-binding domain is a heparin-binding domain
Implementation Method 2
the streptavidin-binding partner is connected to the viral-binding domain
Data Source
AI summary
Provided herein are proteins comprising a viral-binding domain and reagents comprising same. In some aspects, the provided proteins and reagents can be used for the purification of viral particles. In some aspects, the provided proteins and reagents improve the efficiency with which target cells can be transduced. Also provided herein are methods using the provided proteins and reagents, including for purifying viral particles or for transducing cells. Related kits and articles of manufacture are also provided.