AD-PC-TRAIL Cells With Conditional Suicide Gene Safety Control
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Solution Overview
Problem
The safety of treatments using living cells carrying bioactive molecules for therapeutic purposes is uncertain due to potential uncontrolled expansion, risk of malign transformations, and toxicity to the receiving organism, which cannot be predicted or controlled.
Innovation Solution
A method to produce conditionally apoptotic cells by introducing a conditional suicide gene (CSG) into AD-PCs using a retroviral vector, specifically a lentiviral vector, enabling controlled self-elimination of AD-PC-TRAIL cells with a suicide activating agent, ensuring safe and effective antitumor action.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If living cells carrying bioactive molecules are used for therapeutic purposes, then antitumor activity is improved, but safety and control of cell expansion deteriorates
Solution Approach 1:
The patent applies preliminary anti-action by introducing a conditional suicide gene (CSG) into the therapeutic cells before administration. This CSG remains dormant during normal operation but can be activated in advance by a specific compound (suicide activating agent) to induce apoptosis. This preemptive measure allows control of cell fate before harmful effects occur, enabling selective elimination of therapeutic cells if needed while maintaining their antitumor activity during treatment.
Solution Approach 2:
The patent uses an intermediary approach by introducing a conditional suicide gene that acts as a controllable safety mechanism. The CSG serves as an intermediary element between the therapeutic cell and the potential harmful effects of uncontrolled expansion or toxicity. It can be activated or deactivated based on therapeutic needs, providing a mediating control mechanism that balances efficacy and safety.
2Object-affected harmful factors
If conditional suicide gene is introduced into AD-PCs, then safety and controllability are improved, but cell functionality and antitumor action may deteriorate
Solution Approach 1:
The patent applies segmentation by separating the functional components: the TRAIL gene for antitumor activity and the conditional suicide gene for safety control. These are introduced as distinct genetic elements that operate independently. The CSG is designed to remain dormant and not interfere with TRAIL expression or function, thus maintaining antitumor action while adding safety control capability.
Solution Approach 2:
The patent applies local quality by making the suicide gene activation specific and localized to certain conditions rather than affecting all cell functions universally. The CSG is activated only by specific suicide activating agents under controlled conditions, leaving other cell functions including TRAIL-mediated antitumor activity unaffected. This selective activation maintains local functionality while providing global safety 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 method ensures the safe and effective elimination of AD-PC-TRAIL cells when required, minimizing side effects and maintaining antitumor efficacy, while preventing uncontrolled expansion and malign transformations.
Implementation Method 1
The CSG is initially contained in a viral particle that is able to infect the recipient cell and thus integrate the coding sequence within its genome
Implementation Method 2
Its biologically inactive product binds with high affinity to a small biologically inert molecule called AP20187. The binding of two products of iCasp9 to AP20187 results in their dimerization and activation finally leading the cell to death
Implementation Method 3
the Tumor necrosis factor-Related Apoptosis-Inducing Ligand (hereafter TRAIL for short) molecule can induce cell death in diseased tissues
Data Source
AI summary
The method to produce conditionally apoptotic cells comprises modifying a cell population with a phenotype attributable to human adipose tissue-derived pericytes (AD-PC) expressing anti-tumor TRAIL introducing a sequence coding a conditional suicide gene (CSG).