Aug 2026· Molecular Biomedicine· Vol 7· 0 citations· 277 references
Medicine
TL;DR
This review systematically summarizes progress in foundational tools and key supporting technologies of synthetic biology, highlights innovative strategies and clinical value in biosensors, cell therapy, living therapeutics, and smart biomaterials, and provides an in-depth comparison of different chassis cells, delivery vectors, and regulatory circuits in terms of disease suitability, safety, and translational efficiency.
Abstract
Based on the principles of engineering reconstruction and programmable design, synthetic biology is driving a paradigm shift in biomedical diagnosis and therapy from conventional models toward intelligent and precision medicine. By constructing artificial genetic circuits, functional cells, and biomaterial systems both in vitro and in vivo, synthetic biology markedly enhances diagnostic sensitivity, therapeutic targeting, and clinical benefit. In recent years, with the maturation of key technologies such as DNA synthesis and assembly, computational modeling, gene editing, RNA regulation, and protein engineering, synthetic biology has spawned numerous applications with potential for clinical translation in fields such as early screening for pathogens and tumors, programmable cellular immunotherapies, intelligent life-based therapies, and the manufacture of medical biomaterials. Nevertheless, current synthetic biology systems still face critical bottlenecks such as insufficient targeting and editing precision in vivo, poor functional stability of gene circuits, pronounced immunogenicity risks, high manufacturing costs, and lagging ethical and regulatory frameworks. This review systematically summarizes progress in foundational tools and key supporting technologies of synthetic biology, highlights innovative strategies and clinical value in biosensors, cell therapy, living therapeutics, and smart biomaterials, and provides an in‑depth comparison of different chassis cells, delivery vectors, and regulatory circuits in terms of disease suitability, safety, and translational efficiency. The artificial intelligence (AI)-enabled component design, closed-loop intelligent regulation, off‑the‑shelf universal cells, and multimodal theranostic platforms are also discussed. This review offers a systematic framework from technical principles to clinical translation and provides theoretical support and technical guidance for developing next-generation synthetic biology-based diagnostic and therapeutic strategies.
Advanced Therapy Medicinal Products — cell therapies, gene therapies, and tissue-engineered products — are beginning to deliver on the promise of curative medicine: CAR-T therapies double survival in chemotherapy-refractory lymphomas, gene therapies reverse the natural history of spinal muscular atrophy and hemoglobinopathies, and Pluripotent Stem Cell (PSC)-derived islet transplantation renders type 1 diabetic patients insulin-independent. Yet the trajectory from proof-of-concept to equitable, scalable deployment is consistently impeded not only by unresolved biology but also by engineering, manufacturing, logistical, regulatory, and economic bottlenecks that the bioengineering community has not engaged with at the required scale. In this Perspective, grounded in clinical experience across hematological malignancies, monogenic diseases, and metabolic disorders, we identify five rate-limiting bottlenecks where bioengineering intervention is urgently needed and uniquely tractable: scalable and adaptive biomanufacturing; real-time in-process quality control; precise targeted delivery; biomaterial and scaffold engineering for cellular engraftment and immune protection; and data-driven patient stratification constrained by health equity. We argue that the evolving regulatory landscape in Europe — including the European Biotech Act framework and ICH Quality by Design principles — creates structural incentives for engineering-led solutions, and that economic sustainability requires bioengineering to drive down production costs and enable the off-the-shelf transition. We call on the bioengineering community to engage with ATMP translation not as technical support to clinical medicine, but as a constitutive partner shaping its pace, cost, and equity.
Giulia Nieri, Anna Spiller, Stella Federico et al.· Frontiers in Bioengineering...· 0 citations
This review highlights chassis selection, circuit architectures, applications for metabolic diseases and cancer, metabolic bottlenecks, and future directions for precision microbial therapeutics for metabolic disorders and oncology.
Boniface Adakole Onoja, S. A. Agada, Waheeb S. Aggad et al.· Microbiology Research· 0 citations
Despite their promise, significant challenges remain, including low cargo-loading efficiency, batch heterogeneity, limited scalability and the absence of standardized manufacturing and regulatory frameworks, future research must address these barriers to accelerate the clinical translation of exosome-based therapeutics.
Elza Karabagh, Babek Alibayov, Adil Allahverdiyev· Expert Reviews in Molecular...· 0 citations
The rapid pace of innovation in synthetic biology and genome engineering elicits a need to reevaluate systems of oversight to ensure that biosafety and biosecurity safeguards are keeping up. Accordingly, the regulation of nucleic acid synthesis, an enabling technology for synthetic biology and genome engineering, is a current focus of political debate in the United States. However, to develop appropriate governance that neither under- nor overregulates technological development, policy leaders must also appreciate how advances in synthetic biology and genome engineering are being employed in the interests of biosecurity to support human health, manufacturing, food security, ecosystems and the natural environment. Synthetic biology can support the development of new therapeutics and health technologies, alternative biomanufacturing methodologies, food and agricultural innovations, environmental biosensors for monitoring infectious and toxic agents, and interventions aimed at preserving and restoring our natural environment. This Perspective provides an overview of current and potential benefits of synthetic biology and genome engineering, aiming to balance the broader societal discussion of potential risks—particularly in this special issue of the journal—with potential social, economic, and environmental value to individuals and society at large.
C. Chapman, Julie Trolle, Dominika Wawrzyniak et al.· Frontiers in Bioengineering...· 0 citations
The convergence of synthetic biology and nanotechnology has created new opportunities for cancer diagnosis and therapy. Engineered microorganisms exhibit unique tumor-targeting, colonization, and immunomodulatory capabilities, while nanomaterials provide versatile platforms for drug delivery, imaging, and controlled therapeutic release. This review summarizes recent advances in the application of engineered microorganisms and nanomaterials in oncology, with a focus on their mechanisms of action, therapeutic potential, and translational challenges. We discuss the roles of the tumor microbiome in cancer progression, microbial engineering strategies for tumor targeting and immune regulation, and the development of nanomaterial-based delivery systems and immunotherapies. Particular attention is given to microbe-nanomaterial hybrid platforms, which combine the advantages of both systems to enhance therapeutic efficacy and modulate the tumor microenvironment. Finally, key challenges related to biosafety, biocompatibility, regulatory approval, and clinical translation are highlighted. The integration of engineered microorganisms and nanomaterials represents a promising strategy for next-generation precision oncology and may accelerate the development of more effective and personalized cancer therapies.
Using DNA nanostructures as “molecular calipers”, researchers employ Watson-Crick base-pairing principles to precisely define the inter-binding site distances, which allows for perfect topological matching.
