Integrase Enzyme Selective DNA Breaks for Targeted Cell Destruction
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Solution Overview
Problem
Current methods lack effective and specific tools for selectively targeting and destroying specific cell populations, such as cancer cells or virally-infected cells, with minimal side effects, necessitating a novel approach for treating various human diseases.
Innovation Solution
The use of retrovirus-derived integrase enzymes, combined with accessory molecules and integration-promoting agents, is proposed to induce double-stranded breaks in chromosomal DNA of target cells, leveraging specific binding and nuclear translocation to trigger apoptosis in targeted cell populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to destroy target cells, then cell destruction can be achieved, but specificity and selectivity are insufficient leading to side effects
Solution Approach 1:
The patent employs an integrase enzyme as an intermediary agent that specifically recognizes and binds to viral DNA sequences. This enzyme mediates the destruction of virally-infected cells by catalyzing DNA breaks only in cells containing the target viral genome, thereby achieving high selectivity and minimizing side effects on healthy cells.
Solution Approach 2:
The integrase enzyme utilizes the viral DNA itself as a recognition target and substrate. The enzyme's natural ability to bind and process viral DNA sequences allows it to autonomously identify and destroy infected cells without requiring external guidance systems, enhancing both selectivity and efficiency.
2Reliability
If DNA breaks are induced in target cells, then cell death is promoted, but DNA repair mechanisms may counteract this effect
Solution Approach 1:
The patent induces multiple simultaneous DNA breaks in the target cells, overwhelming the cellular DNA repair capacity. By changing the parameter of DNA damage from single isolated breaks to multiple concurrent breaks, the system ensures that repair mechanisms cannot restore genomic integrity, leading to inevitable cell death.
Solution Approach 2:
The integrase enzyme continuously catalyzes DNA breaks in the target cells, maintaining a persistent state of genomic instability. This continuous action prevents the cell from recovering, as new breaks are formed faster than repair mechanisms can act, ensuring complete destruction of DNA integrity.
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 the selective destruction of specific cell populations by overwhelming their DNA repair capabilities, effectively inducing apoptosis and providing a targeted therapy for conditions like cancer and viral infections with reduced side effects.
Implementation Method 1
an integrating enzyme, capable of specific binding to the dsDNA molecule, entering the nucleus of a cell, and creating DSBs in the chromosomal DNA of the cell
Data Source
AI summary
The present invention provides compositions and methods for inducing DNA breaks in specifically-targeted cells, in particular cancer and HIV-infected cells, thereby promoting cell death.