DrBphP Nanobody Light-Induced Dimerization System
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Solution Overview
Problem
Existing red light-induced dimerization systems for clinical applications, such as cell and gene therapies, are limited by complex structures and suboptimal in vivo performance due to their reliance on phytochrome photoreceptors and naturally occurring binding partners.
Innovation Solution
Development of Deinococcus radiodurans bacteriophytochrome (DrBphP) light form-binding antibodies with specific complementarity-determining regions (CDRs) for creating a light-induced dimerization (LID) system, utilizing phage display and yeast two-hybrid screening to select binders that specifically engage the light-activated form of a photoswitchable protein, thereby overcoming the limitations of natural systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If phytochrome photoreceptors and naturally occurring binding partners are used for red light-induced dimerization, then the system can achieve light-controlled protein dimerization, but the structure becomes complex and in vivo performance becomes suboptimal
Solution Approach 1:
The patent divides the photoreceptor system into two separate components: a photosensory module (DrBphP) that undergoes light-induced conformational change, and a binding partner (nanobody) that specifically binds to the light-activated form. This segmentation eliminates the need for complex naturally occurring dimerization interfaces while maintaining light-controlled specificity.
Solution Approach 2:
The patent extracts only the essential photosensory domain (DrBphP) from the full phytochrome protein, removing complex regulatory regions and dimerization interfaces. This extracted photosensory module is then paired with a simplified nanobody binder, achieving light-controlled dimerization with reduced structural complexity.
2Object-affected harmful factors
If existing red light-induced dimerization systems are used, then protein dimerization can be controlled by red light, but tissue penetration depth is limited
Solution Approach 1:
The patent selects DrBphP as the photosensory module, which absorbs red light at wavelengths optimized for tissue penetration. By changing the spectral parameters of the photoreceptor to match the tissue transparency window, the system achieves deeper tissue penetration while maintaining reliable light-controlled dimerization for clinical applications.
3Measurement precision
If naturally occurring binding partners are used, then light-induced dimerization can occur, but specificity and dark activity control are suboptimal
Solution Approach 1:
Instead of using complex naturally occurring binding partners, the patent uses nanobodies - simplified antibody fragments that copy the essential binding function. These nanobodies are engineered to specifically recognize the light-activated conformation of DrBphP, achieving high binding specificity and minimal dark activity control.
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 LID system achieves high specificity and low dark activity, enabling efficient light-induced gene expression and spatiotemporal activation of chimeric antigen receptor T (CAR-T) cells with improved in vivo performance and deep tissue penetration.
Implementation Method 1
Deinococcus radiodurans bacteriophytochrome (DrBphP) light form-binding antibodies
Data Source
AI summary
Deinococcus radiodurans phytochrome (DrBphP) light form-binding antibodies are disclosed and their use in light induced dimerization systems.