RAD51 Modulators for Selective DNA Repair Control

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Solution Overview

Problem

Current methods for modulating RAD51 protein activity in cells are limited in their ability to selectively enhance or inhibit DNA repair processes, particularly in the context of DNA damaging therapies and genomic stability, with existing approaches often affecting both cancerous and non-cancerous cells.

Innovation Solution

Development of compounds that directly modulate RAD51 protein activity by increasing or decreasing its function, allowing for the enhancement of homologous recombination and DNA repair processes, thereby protecting normal cells from DNA damage while sensitizing cancer cells to therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing methods are used to modulate RAD51 protein activity, then DNA repair processes are affected, but both cancerous and non-cancerous cells are affected non-selectively

Engineering Contradiction:
Improveselectivity of DNA repair modulationVSAvoidapplicability to different cell types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by developing compounds that selectively modulate RAD51 activity in specific cell types (cancer cells vs. normal cells). The compounds are designed to target and accumulate preferentially in cancer cells, where they enhance or inhibit RAD51-mediated DNA repair depending on the therapeutic objective, while leaving normal cells with intact DNA repair capabilities.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by creating compounds that can either enhance or inhibit RAD51 protein activity based on desired therapeutic outcomes. By modulating the activity level of RAD51 (a key parameter in DNA repair), the compounds achieve selective effects on cancer cells versus normal cells, improving the therapeutic window for cancer treatments.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If RAD51 activity is enhanced to protect normal cells from DNA damage, then cancer cell sensitivity to therapy may be reduced

Engineering Contradiction:
Improveprotection from DNA damageVSAvoidtherapeutic efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent resolves this contradiction by ensuring that RAD51-modulating compounds are selectively taken up or activated in cancer cells versus normal cells. This spatial selectivity allows the same compound to have different effects in different cell types, protecting normal cells while maintaining cancer cell sensitivity to therapy.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent applies dynamics by creating reversible modulators of RAD51 activity that can be temporarily administered during therapy cycles. The dynamic nature of these compounds allows for temporary enhancement of DNA repair in normal cells during treatment, followed by periods where normal cell repair mechanisms return to baseline, maintaining overall therapeutic efficacy.

Inventive Principle:
Principle #15Dynamics

Data Source

PatentUS9198914B2Methods and compositions for modulating RAD51 and homologous recombination
Publication Date: 2015.12.01 UNIVERSITY OF CHICAGO
  • US9198914B2 patent drawing
  • US9198914B2 patent drawing
  • US9198914B2 patent drawing

AI summary

The present invention concerns methods and compositions involving inhibitors and enhancers of RAD51, a protein involved in homologous recombination. In some embodiments, the present invention concerns methods for stimulating homologous recombination, which has a number of significant research and clinical applications. In certain other embodiments, there are methods for protecting cells using a compound that enhances RAD51 activity. Such enhancers may also be employed to prevent or reduce damage to cells that may be caused by DNA damaging agents. In other embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 enhancer or inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.