INTERNATIONAL CONGRESS OF
CancerGenetics
A Review on the Design of Revolutionary Synthetic Gene Circuits for Precision Gene Editing in Oncology and Cellular Reprogramming
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Sahar Masoomi,1,*
1. Independent Researcher in Medical Genetics, Genetic Engineering, Molecular Oncology, and Medical & Pharmaceutical Biotechnology, focusing on gene therapy and genetic modification for cancer treatment, Founder & Scientific Director, Sabrigen Research Initiative (Virtual Institute under Development),
- Introduction: In recent years, the engineering of synthetic gene circuits has emerged as a novel approach in synthetic biology, attracting significant attention. These circuits, composed of various genetic components such as promoters, operators, enhancer elements, tumor suppressor genes, oncogenes, and reporter genes, enable precise control of cellular behavior through modulation of key signaling pathways, including MAPK and PI3K/AKT. The design of these circuits aims to create new cellular functions, including therapeutic protein production, disease detection, and modulation of cellular behavior. In the context of cancer therapy, synthetic gene circuits have been proposed as an innovative strategy within precision medicine. These circuits can modulate cellular behavior in response to specific tumor characteristics, thereby inhibiting tumor growth, inducing selective apoptosis, and preventing metastasis. Circuits designed to guide immune cells specifically toward tumor sites have been shown to enhance immunotherapy efficacy, including CAR-T and NK cell-based therapies. Cellular reprogramming refers to the process by which cellular identities are altered to transform one cell type into another. The use of synthetic gene circuits in this context provides a tool to direct cellular reprogramming processes, with potential applications in treating genetic disorders, tissue regeneration, and engineering novel tissue constructs. Recent advances in circuit design, integration of lineage-specific transcription factors, and the use of nanomaterials have opened new avenues for clinical translation.
- Methods: In this review, recent advances in synthetic gene circuits for cancer therapy and cellular reprogramming were examined. Open-access articles published between 2019 and 2025 in PubMed, Google Scholar, and PubMed Central were selected, covering synthetic gene circuits, gene editing, cancer therapy, and cellular reprogramming, including review and research articles. Data were analyzed for methodology, findings, and clinical applications to identify emerging trends and opportunities. Data were extracted and analyzed using integrative bioinformatics approaches and single-cell transcriptomic analyses to evaluate circuit performance across diverse cellular contexts. Synthetic gene circuits enable precise control of cellular behavior. A 2024 study demonstrated a circuit targeting cancer cells with aberrant RAS activity without harming normal cells. Circuits also guide stem cell differentiation, as shown in a 2025 study differentiating stem cells into neural cells. Nanomaterials have been shown to enhance delivery, stability, and effectiveness of synthetic gene circuits.
- Results: Recent studies have demonstrated significant advances in the design and application of synthetic gene circuits for cancer therapy and cellular reprogramming. These circuits, based on principles of synthetic biology, allow precise modulation of cellular behavior and oncogenic signaling cascades. In cancer therapy, synthetic gene circuits can specifically target malignant cells while minimizing damage to healthy cells. A 2024 study designed a synthetic gene circuit capable of detecting and targeting cancer cells with aberrant RAS activity without affecting normal cells, highlighting their high therapeutic potential. These circuits can orchestrate apoptosis, inhibit proliferation, and modulate tumor microenvironment interactions, including angiogenesis and immune evasion mechanisms. In cellular reprogramming, synthetic gene circuits guide stem cell differentiation. A 2025 study demonstrated their use in directing stem cells into neural cells, effectively controlling cell fate by regulating lineage-specific transcription factors. Nanomaterials facilitate delivery, enhance circuit efficiency, and improve clinical applicability across diverse cellular models.
- Conclusion: Based on current evidence and recent findings, synthetic gene circuits have emerged as an advanced and revolutionary tool in cancer therapy and cellular reprogramming. By precisely designing genetic components, including promoters, operators, enhancer elements, tumor suppressor genes, oncogenes, and reporter genes, these circuits enable fine-tuned control of gene expression and cellular behavior, allowing targeted regulation of differentiation processes and tumor-related signaling pathways. Studies have demonstrated selective targeting of cancer cells with molecular abnormalities, such as mutant RAS activity, without harming normal cells, and effective guidance of cellular reprogramming and differentiation pathways. Despite challenges such as efficient gene delivery, circuit stability, and precise regulation under diverse microenvironmental conditions, advances in nanomaterials, smart delivery systems, and advanced preclinical models have enhanced the clinical translation potential of synthetic gene circuits. Development and optimization of these circuits are expected to improve targeted and personalized cancer therapies, enable novel approaches in tissue engineering and cellular regeneration, and accelerate transformative progress in precision medicine, modern biotechnology, and cellular immunotherapy. Overall, synthetic gene circuits represent both cutting-edge research tools and forward-looking therapeutic strategies capable of fundamentally reshaping treatment paradigms, cellular engineering approaches, and translational oncology.
- Keywords: Synthetic Gene Circuits, Gene Editing, Oncology, Cellular Reprogramming, Targeted Therapy
