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Updated: Aug 19, 2026
Establishment and Culture of Patient-Derived Breast Organoids
Published on: February 17, 2023
AI-driven CRISPR strategies in breast cancer: Organoid modeling, adaptive editing, and precision delivery
Anmar Ghanim Taki1, Abdulkareem Shareef2, Vimal Arora3
1Department of Radiology Techniques, Health and Medical Techniques College, Alnoor University, Nineveh, Iraq.
Abstract:
Triple-negative breast cancer (TNBC) is defined by profound heterogeneity, dormant metastatic reservoirs, and rapid therapy resistance. Building on our AI-Driven CRISPR Strategies in Breast Cancer framework, CRISPR-Cas9 is emerging as more than a gene-editing tool, capable of restoring circadian integrity, eliminating dormant clones, and re-programming immune surveillance. A structured PubMed, Scopus, and ClinicalTrials.gov review through 2025 integrated mechanistic, preclinical, and early clinical evidence. Beyond standard knockout, base, and prime editing, we highlight chrono-genomic repair of BMAL1/PER2, dormancy-focused synthetic-lethality screens, and genomic-collapse tactics for BRCA1-deficient tumors. Adaptive AI pipelines that iteratively refine guide RNAs and exosome-mimetic carriers, incorporating Boolean logic gates, were also evaluated for self-regulated, tumor-specific delivery. Proof-of-concept studies show that HER2 deletion, TP53 rescue, and ABCB1 silencing enhance chemosensitivity across luminal, HER2-positive, and TNBC models. Circadian restoration expands therapeutic windows and delays relapse in xenografts. Dormancy-directed CRISPR screens reveal unique vulnerabilities in disseminated tumor cells, whereas genomic collapse selectively destroys BRCA1-mutant clones. Integration with CAR-T cells and antibody-drug conjugates amplifies cytotoxicity, and transient nanoparticle or exosome systems improve solid-tumor penetration while minimizing off-target events. CRISPR-Cas9 is transitioning from a molecular scalpel to an adaptive, self-learning therapeutic ecosystem. By uniting AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery, the strategies detailed here define a next-generation precision-oncology paradigm capable of anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse.
Insights
CRISPR-Cas9 gene editing, guided by AI, offers new strategies to combat triple-negative breast cancer (TNBC) by restoring circadian rhythms, targeting dormant cells, and enhancing immune response for improved treatment outcomes.
Area of Science:
- Oncology
- Genetics
- Bioengineering
Background:
- Triple-negative breast cancer (TNBC) presents significant challenges due to its heterogeneity, dormant metastatic cells, and resistance to therapies.
- Current treatment limitations necessitate innovative approaches to overcome therapeutic resistance and prevent metastatic relapse.
Purpose of the Study:
- To explore the potential of CRISPR-Cas9 gene editing, integrated with artificial intelligence (AI), as a next-generation therapeutic strategy for TNBC.
- To review and synthesize evidence on novel CRISPR-Cas9 applications, including chrono-genomic repair, dormancy targeting, and adaptive delivery systems.
Main Methods:
- A comprehensive review of PubMed, Scopus, and ClinicalTrials.gov up to 2025, integrating mechanistic, preclinical, and early clinical data.
- Evaluation of advanced CRISPR-Cas9 editing techniques (knockout, base, prime editing) and novel applications like chrono-genomic repair and synthetic lethality screens.
- Assessment of AI-driven guide RNA refinement, exosome-mimetic delivery systems with Boolean logic gates, and integration with immunotherapy (CAR-T) and antibody-drug conjugates.
Main Results:
- CRISPR-Cas9 strategies demonstrate potential in restoring circadian integrity (BMAL1/PER2 repair), eliminating dormant clones, and reprogramming immune surveillance.
- Proof-of-concept studies show enhanced chemosensitivity via HER2 deletion, TP53 rescue, and ABCB1 silencing in various breast cancer models.
- Circadian restoration delayed relapse in xenografts, while dormancy-directed screens identified unique vulnerabilities and genomic collapse selectively targeted BRCA1-mutant clones.
Conclusions:
- CRISPR-Cas9 is evolving into an adaptive, self-learning therapeutic ecosystem for precision oncology.
- AI-guided design, circadian reprogramming, dormancy eradication, and logic-gated delivery represent a paradigm shift in cancer treatment.
- These integrated strategies hold promise for anticipating tumor evolution, overcoming resistance, and preventing metastatic relapse in TNBC and other cancers.
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