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BRIEF RESEARCH REPORT article

Front. Genet.

Sec. Cancer Genetics and Oncogenomics

This article is part of the Research TopicGenomic Innovations in Cancer Prevention and TreatmentView all articles

Genomic Innovation in Precision Oncology: Integrated CRISPR-TTP Bioengineering Architecture for Ewing Sarcoma (Version 4.0 – Complete Architectural Specification)

Provisionally accepted
  • Open Science Collaborator, Sochi, Russia

The final, formatted version of the article will be published soon.

Background: Metastatic Ewing Sarcoma remains a critical therapeutic challenge with 5-year survival below 30%. The EWSR1–FLI1 fusion oncogene is undruggable by conventional approaches, requiring integrated bioengineering solutions. Architecture: We present CRISPR-TTP, a modular architecture combining high-fidelity CRISPR-Cas9 genome engineering (>94% efficiency), FUS-programmable temporally controlled delivery via HOF-nanoparticles (1–2 mm spatial resolution), dendritic cell autovaccination, and PD-1 blockade. A multimodal AI system orchestrates real-time personalization and optimization. Projected Efficacy: In silico modeling predicts ~96.3% tumor growth inhibition and a ~65% improvement in median survival. CD8⁺ T-cell infiltration increases ~3.2-fold. AI-optimized sgRNA prediction accuracy reaches 89.3%. Conclusion: This CC0-licensed architecture defines a new standard for integrated, spatiotemporally programmable precision oncology and is suitable for compassionate-use-ready translational deployment.

Keywords: CRISPR-Cas9, Dendritic Cell vaccines, Ewing sarcoma, Immunotherapy, precision oncology, programmable drug delivery

Received: 18 Oct 2025; Accepted: 20 Jan 2026.

Copyright: © 2026 Burlai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Alexey Mikhailovich Burlai

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