Temperature-Sensitive Viral Vectors for Transient Gene Expression
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Solution Overview
Problem
Current gene therapy methods face challenges in achieving transient, short-term expression of therapeutic genes, as continuous expression can be harmful and existing delivery methods are inefficient and cumbersome.
Innovation Solution
The use of temperature-sensitive agents, such as ts-RNA or ts-protein molecules, encoded by heterologous nucleic acids in temperature-sensitive viral vectors or self-replicating RNAs, which are activated at a permissive temperature and inactivated at a non-permissive temperature, allowing for controlled transient expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional viral vectors are used for gene therapy, then continuous expression of therapeutic genes is achieved, but harmful long-term expression effects occur
Solution Approach 1:
The patent applies parameter changes by modifying the temperature sensitivity parameter of the viral vector. The temperature-sensitive viral vector allows the system to switch between functional and non-functional states based on temperature, enabling controlled transient expression of therapeutic genes without continuous expression effects
Solution Approach 2:
The patent implements periodic action through transient expression cycles. The therapeutic gene is expressed in periodic bursts at permissive temperatures rather than continuously, allowing the system to achieve therapeutic effects while avoiding harmful cumulative effects of continuous expression
2Duration of action of moving object
If synthetic mRNA delivery methods are used for transient expression, then short-term gene expression is achieved, but delivery efficiency and protein product sufficiency are limited
Solution Approach 1:
The patent applies dynamics by creating a self-replicating system where the mRNA can dynamically increase its own copies within the cell. The self-replicating RNA mechanism allows the system to adapt and amplify protein production over time, transforming a static delivery problem into a dynamic self-amplifying process
Solution Approach 2:
The patent implements self-service through self-replicating RNA that can autonomously amplify itself and produce multiple copies of the therapeutic protein. The system serves itself by using its own genetic material to create more copies, eliminating the need for repeated external deliveries
3Quantity of substance
If repeated mRNA transfection is performed to maintain protein levels, then sufficient protein product is achieved, but the process becomes cumbersome and inefficient
Solution Approach 1:
The patent applies preliminary action by equipping the mRNA with self-replicating capabilities before delivery. This preliminary modification allows the delivered RNA to automatically generate sufficient protein levels through self-amplification, eliminating the need for subsequent repeated transfections
Solution Approach 2:
The patent implements continuity of useful action through self-replicating RNA that maintains continuous protein production within the cell. The system sustains therapeutic protein levels over extended periods through internal replication mechanisms, replacing the need for intermittent external deliveries
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
This approach enables biologically meaningful effects with controlled transient expression of therapeutic agents, reducing the risk of harmful long-term expression and improving delivery efficiency.
Implementation Method 1
temperature-sensitive agents, such as ts-RNA or ts-protein molecules, encoded by heterologous nucleic acids in temperature-sensitive viral vectors or self-replicating RNAs, which are activated at a permissive temperature and inactivated at a non-permissive temperature
Data Source
AI summary
The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.