Optically Controlled Virus Vector for Gene Therapy
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Solution Overview
Problem
Current gene transfer technologies using virus vectors lack control over virus vector activity after infection, leading to side effects and risks of vector persistence in body tissues.
Innovation Solution
Incorporating a gene coding for an optical switch protein into a virus protein, allowing enzyme activity control through light irradiation, specifically by inserting the optical switch protein into an exogenous gene-transferable region of a virus protein with multiple functional domains.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If virus vectors are used for gene transfer, then transfer efficiency and expression efficiency are improved, but control over virus vector activity after infection is lost leading to side effects and vector persistence
Solution Approach 1:
The patent applies dynamics by making the virus vector activity controllable and adjustable after infection through light irradiation. The optical switch protein (e.g., Dronpa, Dendra2, mEos) integrated into the virus vector allows the vector to transition between active and inactive states dynamically, enabling post-infection control of viral replication and gene expression without permanently compromising the vector's function.
Solution Approach 2:
The patent utilizes parameter changes by employing optical switch proteins that change their functional state in response to light irradiation parameters (wavelength, intensity, duration). This allows precise control of virus vector activity by adjusting light parameters, enabling the system to switch between different activity levels and states, thereby resolving the contradiction between maintaining high transfer efficiency and achieving reliable post-infection control.
2Productivity
If retrovirus is used for integration into genome, then gene transfer is achieved, but the virus remains after integration completing resulting in side effects
Solution Approach 1:
The patent extracts the harmful persistence property of retroviruses by integrating an optical switch protein that enables selective inactivation. The optical switch component allows the viral integrase or related proteins to be deactivated after successful integration, extracting the harmful persistent activity while preserving the beneficial integration function. This enables the system to achieve gene integration while eliminating subsequent harmful effects.
Solution Approach 2:
The patent converts the harmful persistence of viral proteins into a beneficial controlled feature by using optical switch proteins. The same viral proteins that cause harmful persistence are equipped with light-controlled on/off switches, transforming the uncontrolled harmful effect into a controllable feature that can be activated for integration and then deactivated to prevent side effects, thereby converting harm into a manageable and beneficial system.
3Productivity
If adenovirus or adeno-associated virus is used for transient gene expression, then gene expression is achieved, but risk of virus remaining in body tissues and vector rescue occurs
Solution Approach 1:
The patent applies preliminary action by pre-equipping the viral proteins with optical switch capabilities before infection. This allows the system to be programmed with the ability to self-inactivate after performing its function, enabling transient expression while preventing persistence and rescue through预先 integrated light-controlled switches that can be activated to terminate viral activity.
Solution Approach 2:
The patent implements feedback control through optical switch proteins that respond to light irradiation. The system provides feedback control over viral activity, where light irradiation serves as the control signal that feeds back to modulate viral protein function. This feedback mechanism enables real-time control of viral persistence and prevents vector rescue by allowing operators to terminate viral activity when desired.
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 regulated enzyme activity of the virus protein, controlling virus vector activity and proliferation through light irradiation, thereby reducing side effects and facilitating safer gene therapy applications.
Implementation Method 1
by inserting a gene coding for an optical switch protein into an exogenous gene-transferable region of a virus protein including multiple functional domains, it is possible to control the enzyme activity of the virus protein by irradiation of light
Data Source
AI summary
The purpose of the present invention is to develop a virus vector, the activity of which is rendered controllable. A virus protein gene derived from an RNA virus is provided in which a gene encoding an optical switch protein is inserted into a foreign gene introducible region of the virus protein so as to enable expression of the gene. By means of this virus vector, it is possible to control, with irradiation of light, enzyme activity of the virus protein and virus vector activity based thereon.