Sequence-Specific DNA-Damaging Agents for Cancer Targeting

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Solution Overview

Problem

Current cancer treatments, such as chemotherapy and radiation, are non-specific and have a narrow therapeutic window, leading to side effects in both cancer cells and normal cells, with few validated biomarkers for response, necessitating a more targeted and patient-specific approach.

Innovation Solution

Development of sequence-specific DNA-damaging agents that target cancer-specific DNA variations, such as copy number amplifications and polymorphisms, using technologies like CRISPR-Cas9 to induce site-specific DNA damage, allowing for preferential killing of cancer cells while sparing normal cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If non-specific chemotherapy agents are used to treat cancer, then cancer cells are killed, but normal cells are also damaged causing side effects

Engineering Contradiction:

Improvecancer cell killing efficacyVSAvoidside effects on normal cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing DNA targeting agents with sequence-specific recognition elements that distinguish cancer-specific DNA sequences from normal DNA sequences. The agents are engineered to bind only to unique genetic markers present in cancer cells, thereby concentrating the therapeutic effect locally at the cancer cell level while leaving normal cells unaffected. This resolves the contradiction by making the killing action specific to cancer cells rather than affecting all dividing cells.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent segments the DNA molecule into specific targetable regions by identifying and isolating cancer-specific DNA sequences (such as mutated genes, amplified regions, or unique chromosomal arrangements). By focusing the therapeutic agent on these segmented, specific DNA regions rather than causing general DNA damage, the treatment achieves cancer cell specificity. This segmentation approach allows the drug to recognize and bind only to the unique genetic fingerprint of cancer cells.

Inventive Principle:

Principle #1Segmentation

2Reliability

If high doses of chemotherapy are administered to overcome resistance, then treatment efficacy improves, but toxicity to normal cells increases

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtoxicity to normal cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs local quality by engineering DNA targeting agents with high affinity and specificity for cancer-specific DNA sequences. The agents are designed to bind tightly and selectively to unique genetic markers in cancer cells, enabling effective treatment at lower doses. This specific binding ensures that even at low concentrations, the therapeutic effect is concentrated on cancer cells, achieving high treatment efficacy without the need for high doses that would toxic to normal cells.

Inventive Principle:

Principle #3Local quality

3Ease of operation

If conventional chemotherapy is used without biomarker validation, then treatment can be administered broadly, but response prediction is poor leading to unnecessary side effects

Engineering Contradiction:

Improvetreatment accessibilityVSAvoidresponse prediction accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by implementing biomarker detection and validation steps before administering the DNA targeting therapy. The treatment protocol includes preliminary identification of cancer-specific DNA sequences through genomic analysis, followed by selection of appropriate targeting agents based on the patient's tumor profile. This preliminary characterization ensures that only patients with matching cancer-specific markers receive the treatment, improving response prediction accuracy while maintaining ease of operation through standardized diagnostic workflows.

Inventive Principle:

Principle #10Preliminary action

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 expands the therapeutic window, enabling higher doses of cancer-specific therapy with reduced side effects by selectively targeting cancer cells, potentially overcoming resistance mechanisms and improving treatment efficacy.

Implementation Method 1

gene targeting for instance by CRISPR/Cas

Methodology Applied

Scientific EffectCRISPR-Cas9 genome editing:

Implementation Method 2

work by inducing DNA-damage that is not adequately repaired by cancer cells

Methodology Applied

Scientific EffectDNA damage induction:

Data Source

PatentUS11492670B2Compositions and methods for targeting cancer-specific sequence variations

Publication Date: 2022.11.08 THE BROAD INST INC

AI summary

The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non-cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.