最新刊期
卷 7 ， 期 1 ， 2026
诊疗合成生物学
张先恩，崔宗强，门冬
Editorial
- 摘要：The CRISPR/Cas system has emerged as a pivotal tool in molecular diagnostics due to its high specificity, programmability, and ease of use. This review provides a comprehensive overview of the mechanistic principles, diagnostic platform optimization, and applications of CRISPR/Cas systems in precision medicine. We begin with an outline of the classification and molecular mechanisms of CRISPR/Cas systems, highlighting the functional differences among Type Ⅰ-Ⅵ systems. Our focus then shifts to innovative diagnostic strategies, including nucleic acid pre-amplification methods (e.g., SHERLOCK, DETECTR) and amplification-free approaches. These strategies have significantly enhanced the sensitivity and specificity of molecular diagnostics, making them more efficient and reliable than conventional techniques. The review then explores the broad clinical applications of CRISPR/Cas technology with infectious diseases, such as pathogen screening and drug-resistance detection, demonstrating remarkable utilization in rapidly identifying pathogens and their resistance profiles. In the field of cancer research, the technology has shown great potential in early screening and genetic variant analysis, which are crucial for developing personalized treatment strategies. Moreover, CRISPR/Cas systems are expanding their diagnostic capabilities to include non-nucleic acid biomarker detection, further solidifying their position as versatile tools in clinical diagnostics. The review also addresses future directions in the field, such as the development of miniaturized devices and high-throughput intelligent diagnostic systems. These advancements are expected to enhance portability, accessibility, and efficiency, enabling rapid point-of-care testing in diverse settings, including resource-limited environments. The integration of CRISPR technology with microfluidics and portable detection devices is particularly promising for enabling rapid and accurate diagnostics at the bedside or in the field. As research continues to evolve, the ongoing refinement of CRISPR/Cas systems is anticipated to significantly improve the accuracy, speed, and accessibility of molecular diagnostics. This progress is expected to lead to better clinical outcomes and more effective public health responses. However, several challenges in clinical translation must be addressed, such as standardization of sensitivity and cost reduction. This review aims to provide a theoretical basis for advancing CRISPR-based diagnostics in biomedical research and to guide the future development of CRISPR/Cas technologies in molecular diagnostics, particularly in overcoming the limitations of traditional diagnostic methods.关键词：CRISPR/Cas system;point-of-care testing;clinical translational applications;miniaturized devices;artificial intelligence assisted molecular diagnosis67|21|0更新时间：2026-03-07
- 摘要：Synthetic biosensors leverage genetically encoded biorecognition components for specifically identified targets and convert them into quantifiable biological signals. These signals can then be processed through genetic circuits to achieve customized signal processing and produce multi-modular signal outputs. Synthetic biosensors offer several compelling advantages including high biocompatibility, low cost, and sustainability, which have shown significant application potentials in environmental monitoring, biomanufacturing, and precision diagnostics. Advances in synthetic biology methods and technological developments, particularly the adoption of various engineering design principles, genetic circuit-enabled programmable signal processing, and AI-assisted mining, and de novo design of biological components, have provided unprecedented momentum for developing new generation synthetic biosensors. However, the practical applications of synthetic biosensors have been restricted by certain technical limitations in sensing performance including sensitivity, specificity, speed, stability, and biosafety, termed as the “5S” challenges. Here we summarize the signal recognition mechanisms and design principles of representative genetic circuit-enabled synthetic biosensors, and provide an in-depth analysis of their technical advantages and remaining challenges. Furthermore, we highlight typical genetic circuit-enabled functional expansion modules for myriad application scenarios. Finally, we introduce the key features of synthetic biosensors and the latest optimization methods for improving sensing performance. We conclude by discussing the challenges and opportunities for accelerating the development of new generation synthetic biosensors for achieving sustainable, affordable, and reliable detection in diverse settings.关键词：synthetic biosensor;genetic circuit;allosteric transcription factor;two-component system;Riboswitch;riboregulator;CRISPR/Cas53|16|0更新时间：2026-03-07
- 摘要：Deoxyribonucleic acid (DNA) molecules store and transmit genetic information in all living organisms and some viruses. In vitro, it can be utilized as a programmable and versatile molecular self-assembling building block to construct functional materials. On the basis of the DNA double helix model and the specific rules of base complementary pairing, where adenine (A) with thymine (T) and cytosine (C) with guanine (G), researchers have developed various DNA self-assembly techniques over the past few decades, including DNA tiling arrays such as DNA origami and laterally developed single strand tiling. These technologies have been employed to construct a variety of two- or three-dimensional nanoscale structures and devices with controllable sizes and morphologies, as well as dynamic response properties to external environmental stimulus. Researchers have continually demonstrated the exceptional construction capabilities of DNA molecules and have constructed a variety of DNA nanostructures: from simple four-arm nucleic acid junction to origami arrays up to 2～3 microns in size, from two-dimensional planar shapes to three-dimensional complex and twisted structures, and from simple nano-tweezers to command-executing DNA walkers. Due to the unparalleled programmability, precise addressability, editable biological functions, tissue permeability and inherent biocompatibility of DNA nanostructures, they have hold significant potentials in molecular biology research such as biosensing, bioimaging, tissue engineering, and drug delivery. In this review, first, we summarize the construction of two- and three-dimensional DNA nanostructures using various DNA self-assembly technologies. Then, the dynamic transformation of DNA nanostructures driven by two distinct types of driving forces have been categorized and discussed. Finally, the prospects of biosensors based on DNA self-assembly technologies, as well as challenges in this field including enhancing the efficiency and stability of synthesized structures, advancing dynamic monitoring technology in vivo, establishing multiplex and rapid detection methods, and exploring new directions for integration with CRISPR technology, have been explored.关键词：DNA self-assembly;2D DNA nanostructure;3D DNA nanostructure;dynamic DNA nanostructure;biosensing;biomarkers40|12|0更新时间：2026-03-07
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Antibody probes in biomolecular sensing： from carbon-based computing to silicon-based computing 封面论文
摘要：The precise recognition, detection, and analysis of protein biomarkers are essential for disease diagnosis and life sciences research. Antibody probes, known for their high specificity and stability, are crucial to biomolecular sensing assays. Traditionally, antibody development has relied on “carbon-based” approaches using animal immune systems. However, we are currently undergoing a transformative shift toward “silicon-based” methods driven by artificial intelligence (AI). Conventional techniques, such as animal-based antibody production and phage display-based directed evolution, have long been challenged by low efficiency and limited control over epitope specificity and binding affinity. Recent AI advances, including de novo protein design and deep learning-driven protein binding protein (PBP) generation, are revolutionizing antibody development. These innovations enable the rapid creation of protein-based biosensing probes (e.g., antibodies and nanobodies) with enhanced specificity and affinity, along with accurate predictions of epitopes and structural features. By overcoming limitations with traditional methods, AI-driven technologies offer unprecedented control over the design and performance of antibody probes. Furthermore, “silicon-based evaluation” plays a key role in PBP generation, allowing for quantitative assessment of binding affinity, stability, and robustness. AI-designed biosensing probes offer potentials for capturing a broader spectrum of biomolecular information, which may be able to detect variations in sequence and conformation, post-translational modifications, abnormal polymerization, and shifts in biological activity. In certain diseases, the abnormal dissociation of multimeric proteins can reveal previously concealed antigenic epitopes, creating disease-specific targets, which can be better addressed with AI-designed probes for more accurate and nuanced insights. Moreover, modern high-performance biomolecular sensing technologies, such as bead-based chemiluminescent immunoassays (CLIA), digital immunoassay, microfluidic immunoassay, and single molecule binding kinetics assays, require highly diverse antibody specificity and affinity, and AI-based protein design tools can meet these divergent needs, enabling the integration of AI-engineered biosensing probes with next-generation sensors. This integration not only enhances detection sensitivity, but also expands the scope of molecular information that can be analyzed. Such a paradigm shift represents a new era in biomolecular sensing, and offers exciting prospects for precision medicine and synthetic biology.关键词：immunoassay;antibody designing;carbon-based computing;artificial intelligence;biosensors72|12|0更新时间：2026-03-07 - 摘要：In recent years, significant advances have been made in genetically encoded fluorescent sensors. Fluorescent protein-based sensors have seen continuous improvements in performance, with researchers employing protein engineering techniques to develop brighter and more photostable fluorescent protein variants, as well as extending their emission spectra into the far-red region for deeper tissue imaging. Concurrently, innovative sensing mechanisms have emerged, such as the incorporation of genetically encoded unnatural fluorescent amino acids to construct miniaturized fluorescent reporter molecules, and strategies utilizing protein conformational changes or Förster resonance energy transfer (FRET) to sensitively detect biological signals. Researchers have also developed highly specific fluorescent sensors targeting particular biomarkers, including genetically encoded sensors for detecting ions, metabolites, or enzyme activities, providing powerful tools for precise monitoring of cellular physiological processes. Meanwhile, RNA fluorescent aptamers, another major category of genetically encoded sensors, have achieved substantial progress in structural optimization and functional expansion. Newly screened and engineered fluorescent aptamers exhibit enhanced affinity and specificity toward their fluorescent ligands, significantly improving fluorescence activation efficiency. Certain aptamer-ligand complexes now exhibit brightness comparable to, or even exceeding, traditional fluorescent proteins. Various combinations of aptamers and fluorophores currently cover emission spectra ranging from visible to near-infrared. These RNA-based sensors have successfully enabled the labeling and visualization of endogenous RNA molecules in living cells, facilitating real-time tracking of RNA localization and dynamics. Furthermore, combining fluorescent aptamers with small-molecule recognition aptamers has enabled the creation of novel fluorescent “switch” sensors, whose fluorescence is activated through conformational changes triggered by the presence of specific metabolites. Both types of genetically encoded sensors demonstrate substantial values in disease diagnosis. For instance, fluorescent protein-based biosensors can monitor abnormal fluctuations of intracellular metabolites and signaling molecules, such as glucose or ATP levels, aiding in the elucidation of metabolic characteristics in diseases like diabetes and cancers. Utilizing improved near-infrared fluorescent proteins and fluorescent aptamers in vivo allows deeper tissue penetration and facilitates early detection of pathological changes, such as tumors. Additionally, fluorescent sensors specifically designed for pathological states-such as oxidative stress, pH imbalance, or particular enzyme activities—can directly report disease signals at the cellular level, supporting precise diagnostics. Overall, these advancements significantly enhance the sensitivity and specificity of biological imaging and molecular diagnostics. Looking forward, as sensor performance continues to improve and new sensing principles emerge, genetically encoded fluorescent sensors will increasingly play prominent roles in more complex biological systems and clinical diagnostics, exhibiting tremendous potentials for future applications.关键词：genetically encoded fluorescent sensors;fluorescent proteins;fluorescent RNA;molecular imaging;disease diagnosis56|9|0更新时间：2026-03-07
- 摘要：Cervical cancer remains a significant global threat to women’s health, responsible for approximately 600 000 new cases and 310 000 deaths worldwide in 2020. This highlights the urgent clinical need for more precise diagnosis and treatment. The current “three-step” screening strategy incorporates testing for high-risk human papillomavirus (HPV), one of the primary causative agents for cervical cancer. However, this approach is hampered by a high false-positive rate, as HPV infection is not sufficient and necessary conditions for the onset and progression of cervical cancer; only a small proportion of infected women can develop cervical intraepithelial neoplasia (CIN) or cancer, which often leads to overdiagnosis and overtreatment. Consequently, there is a pressing need, emphasized by recent WHO guidelines, to develop effective and functionally well-defined molecular biomarkers to improve the precision of clinical triage and diagnosis. This review addresses two critical bottlenecks impeding the discovery and translation of such biomarkers. The first is the lower effectiveness of existing technologies to overcome the challenge of tumor heterogeneity, where the molecular signals of critical malignant cell subpopulations are often obscured in bulk tissue analyses. The second bottleneck is the limitation of current detection methods used for validation, which often lack of the sensitivity, quantitative reliability, and throughput required for robust clinical verification. To overcome these obstacles, we propose a research framework that integrates single-cell omics with advanced biosensing technologies. This framework first leverages single-cell transcriptomics to decipher tumor heterogeneity at an unparalleled resolution, enabling the discovery of higher-quality biomarker candidates by identifying gene expression signatures unique to the specific subgroup of cells driving malignant progression. Subsequently, these candidates are validated using biosensing systems engineered through synthetic biology principles, such as high-sensitivity in situ hybridization for quantitative tissue analysis and novel CRISPR-Cas-mediated nucleic acid detection technologies. These advanced platforms may offer programmable, ultra-sensitive, and highly specific detection of biomarkers in clinical samples. By synergizing high-resolution discovery with high-fidelity validation, this framework may not only facilitate a more complete characterization of novel biomarkers, but also provides a direct pathway for translating these biosensing platforms into scalable clinical diagnostic kits. These technologies may serve as key drivers to enhance the early detection and precise management of cervical cancer.关键词：cervical cancer;cancer molecular markers;biosensing;single-cell transcriptome;precision medicine47|3|0更新时间：2026-03-07
- 摘要：RNA vaccines have emerged as a revolutionary technology in vaccinology due to their rapid development and high immunogenicity. This article systematically reviews the latest research progress in molecular design and delivery systems of mRNA vaccines, with a focus on three major types: linear mRNA, circular RNA (circRNA), and self-amplifying RNA (saRNA). It highlights that mRNA vaccines, with their rapid development, high immunogenicity, and favorable safety profiles, have become a significant breakthrough in vaccine technology, demonstrating immense potentials, especially during the COVID-19 pandemic. In terms of design optimization, linear mRNA improves its stability and translation efficiency through strategies such as 5′cap, untranslated region (UTR) optimization, codon selection, and poly(A) tail elongation. Circular RNA, with its covalently closed circular structure, exhibits excellent resistance to nucleases and long-lasting expression properties, providing a new avenue for sustained antigen presentation. Self-amplifying RNA leverages viral replication mechanism to achieve intracellular self-replication, significantly reducing vaccine dosage requirements and enhancing immune responses. The article also notes that while mRNA vaccines inherently possesses certain immune-stimulatory effects (acting as a built-in adjuvant), excessive activation of innate immunity may compromise their efficacy. Thus, balancing immunogenicity and expression efficiency requires modifications of nucleotides (e.g., pseudouridine, N1-methyl-pseudouridine) and purification processes (e.g., HPLC, FPLC). As for the delivery systems, lipid nanoparticles (LNPs) remain as the mainstream platform. Through the rational composition of ionizable lipids, phospholipids, cholesterol, and PEGylated lipids, LNPs achieve efficient mRNA encapsulation and prevent endosomal escape. Additionally, virus-like particles, as an emerging bioinspired carrier, show great promise with their natural hollow structure, self-assembly properties, and high biocompatibility, enabling enhanced uptake efficiency by antigen-presenting cells and mimicking viral invasion pathways. Other delivery strategies, such as polymer nanoparticles, peptide/protein carriers, and ex vivo dendritic cells loading, are also being continuously optimized. This article further explores the tremendous potential of mRNA vaccines in personalized cancer therapy and the prevention of broad-spectrum infectious diseases. It also identifies current challenges, including formulation stability (reliance on cold chains), limited targeting specificity, high production cost, and the regulation of prolonged immune response. Looking ahead, the integration of interdisciplinary innovations—such as artificial intelligence for sequence optimization, development of novel lyophilization techniques, and modular manufacturing—will gradually overcome existing limitations, advancing mRNA vaccine technology toward a more precise, safe, and efficient next-generation platform. This progress will not only play a vital role in human medicine, but also promote the implementation of the “One Health” strategy in veterinary medicine.关键词：RNA vaccine;circular RNA (circRNA);self-amplifying RNA (saRNA);vaccine design;delivery system;lipid nanoparticles (LNPs);virus-like particles (VLPs)20|3|0更新时间：2026-03-07
- 摘要：Vaccines, as a cornerstone of infectious disease prevention and control, have undergone four transformative revolutions throughout their development and applications. In recent years, the rapid advancement of computational technologies has further propelled vaccine development into a new era, giving rise to a synthetic biology paradigm centered on structure-guided protein optimization and computational design. This article systematically reviews the applications and significance of three key protein optimization strategies—directed evolution, semi-rational design, and rational design—as well as de novo protein synthesis, with a focus on their roles in vaccine development. At the immunogen design level, strategies such as structural stabilization, epitope focusing, and glycosylation modulation are discussed for their potentials to enhance antigen immunogenicity and broaden protective efficacy. At the delivery system level, the unique advantages of protein nanoparticles in eliciting cross-neutralizing antibody responses are emphasized. These nanoparticles utilize high-density antigen presentation and precise geometric conformations, combined with “mosaic” multivalent display technology. Advances in artificial intelligence based computational tools have facilitated a paradigm shift from “structural simulation” to “functional customization”, thereby significantly promoting the development of structure-guided reverse vaccinology based on antigen-antibody complex structures. The integration of computational epitope screening and de novo protein backbone design has facilitated a transition from natural structures to customized designs in vaccine development. Although challenges remain, such as achieving broad-spectrum protection against highly variable pathogens and accurately simulating dynamic conformations, the deep synergy between vaccine design and computational tools has significantly accelerated the clinical translation of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV), and established a universal design framework for the prevention and control of future emerging and unknown infectious diseases.关键词：protein optimization;de novo design;vaccine design;nanoparticle vaccine;reverse vaccinology27|5|0更新时间：2026-03-07
- 摘要：Cell membrane-derived nanoparticles (CNPs) integrate the biological characteristics of natural cell membranes (e.g., immune evasion, lesion targeting and immune modulation) for the tailorable physicochemical properties of synthetic nanomaterials, demonstrating significant advantages such as prolonged circulation, high biocompatibility, and specific targeting in disease diagnosis and treatment. However, their clinical applications are limited by the inherent heterogeneity and functional limitations of natural membranes, including restricted targeting specificity, uncontrollable responsiveness, and lack of functionality. Synthetic biology provides innovative strategies to overcome these bottlenecks, driving a paradigm shift in CNPs from natural biomimicry to precise design. Genetic engineering enables precise editing of cell membrane protein expression via physical (e.g., electroporation, microinjection, and gene gun), chemical (cationic lipids/polymers), and biological (viral vectors) strategies. Concurrently, metabolic engineering regulates the directional anchoring of functional moieties on cell membranes through manipulating cells’ natural biosynthetic pathways, such as glycan (sialic acid and N-acetylgalactosamine (GalNAc) salvage pathways) and lipid (cytidine 5'-diphosphocholine pathway) metabolism. These approaches endow CNPs with enhanced targeting specificity, intelligent responsiveness (e.g., pH/enzyme/light-triggered drug release), and multifunctional synergy, enabling them to demonstrate significant therapeutic potentials on diverse diseases including malignant tumors, cardiovascular diseases, and infectious diseases. In oncology, synthetic CNPs (SCNPs) deliver chemotherapeutics, radiotherapy sensitizers and contrast agents with tumor-homing specificity and enable innovative immunotherapies by presenting checkpoint inhibitors, tumor antigens or adjuvants. For cardiovascular diseases, SCNPs demonstrate remarkable inflammatory targeting and alleviation capabilities. In infectious diseases, SCNPs neutralize toxins, bacteria, and viruses as broad-spectrum “nanosponges”, while antigen-presenting SCNPs act as potent vaccines. Applications of SCNPs extend to autoimmune conditions, neurodegenerative disorders, and bone-related diseases. Although challenges remain in safety assessment, scalable manufacturing, and regulatory framework, advances in artificial intelligence-assisted rational design, novel gene editing tools (e.g., prime editing) for safer genomic modifications, metabolic intervention technologies, alongside the establishment of standardized production platforms, are poised to bridge the gap between laboratory research and clinic practice. Ultimately, synthetic biology-powered CNPs are anticipated to be evolved into intelligentnano-theranostic platforms facilitating precision medicine.关键词：cell membrane-derived nanoparticles;synthetic biology;genetic engineering;metabolic engineering;precision medicine26|3|0更新时间：2026-03-07
- 摘要：As novel photon upconversion materials, the low excitation intensity, high upconversion quantum efficiency, and tunable absorption/emission wavelengths of triplet-triplet annihilation upconversion (TTA-UC)-based materials are a promising candidate for biomedical applications. These materials facilitate the conversion of low-energy photons to high-energy emissions through a bimolecular absorption process, which is regulated by the triplet-triplet energy transfer (TTET) of photosensitizers and the triplet-triplet annihilation (TTA) of annihilators. TTA-UC’s cutting-edge applications, including deep-tissue imaging, targeted photodynamic therapy (PDT), and precise optogenetic, are characterized by their nonlinear optical properties, which enable them to surpass the penetration depth constraints of conventional fluorescent materials. However, molecular oxygen (3O2) induces non-radiative decay pathways, resulting in severe quenching effects that significantly reduce upconversion quantum efficiency, particularly in physiological environments. In the past decade, researchers worldwide have developed a variety of innovative strategies to mitigate the oxygen-quenching effect to address this technical barrier. This review provides a comprehensive overview of the current scientific approaches for the development of high-performance and oxygen-resistant TTA-UC materials, with an emphasis on the elucidation of their underlying working mechanisms: (1) The stabilization of TTA-UC pairs through synergistic electron-deficient group modifications and molecular conformation engineering to improve photostability; (2) Oxygen-resistant TTA-UC nanoparticles can be achieved through reductive oil-droplets as soft cores; (3) The kinetics of intermolecular triplet energy transfer can be optimized for oxygen tolerance through microstructural regulation. These approaches are critically assessed with respect to their advantages and disadvantages. Additionally, this review evaluates primary obstacles that TTA-UC nanoparticles face, such as the improvement of TTA-UC efficacy in the near-infrared region and the development of novel TTA-UC nanoparticle preparation strategies and surface bioconjugate chemistry. It is suggested that TTA-UC be integrated with synthetic biology to facilitate the development of biosynthesized upconversion proteins, favor the establishment of upconversion luminescence as a fundamental tool in life sciences, and facilitate its practical implementation across multiple biomedical fields in the near future.关键词：triplet-triplet annihilation upconversion;photoredox;nanoparticles;biosynthesis;nanobiotechnology20|2|0更新时间：2026-03-07
- 摘要：Artificial blood refers to oxygen-carrying liquid formulations that can partially substitute the functions of blood. Its development seeks to lessen reliance on donor supplies, alleviate shortages, and reduce transfusion-related risks. In recent years, advances in synthetic biology have driven notable progress in both the functional reconstruction and the system-level integration of the principal components of artificial blood—red blood cells, platelets, and plasma. Taking a synthetic-biology perspective, this review summarizes construction strategies and recent advances in these aspects. For artificial red blood cells, three complementary strategies have be proven to be highly effective: the rational optimization of hemoglobin structure, the reconstruction of heme-biosynthetic pathways to balance cofactor supply with globin expression, and biomimetic membrane encapsulation. Together, these strategies enhance oxygen-delivery efficiency and improve in vivo stability. In the platelet module, stem-cell programming and gene programming have markedly increased production efficiency, offering a path toward more controllable and scalable sources that are independent of donor availability. For artificial plasma, optimizing the expression of core functional proteins and designing multifunctional fusion proteins provide new possibilities for maintaining circulating volume and supporting immune function. The review also discusses key challenges that currently limit the translation. Present research remains largely focused on single functional modules, and substantial bottlenecks persist in biocompatibility, long-term stability, large-scale manufacturing, and the establishment of robust quality-standard systems. Addressing these gaps require standardized evaluation criteria spanning safety, potency, and stability, alongside reproducible processes suitable for clinical-grade production. In the future, the field can leverage modular design principles in combination with artificial-intelligence assistance to integrate red-cell, platelet, and plasma functions into coherent, programmable architectures. Such integrative strategies are expected to accelerate the pathway from laboratory concepts to clinical applications and to support the development of safer and more effective next-generation blood substitutes. By integrating synthetic-biology toolkits with rigorous quality control and scalable production, artificial blood research is poised for clinical translation. This progress promises practical solutions for oxygen transport, volume maintenance, and immune support in settings with limited blood supplies or high transfusion risks.关键词：artificial blood;synthetic biology;artificial red blood cells;artificial platelets;plasma substitutes18|5|0更新时间：2026-03-07
- 摘要：Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) has been identified as a reliable marker for adult stem cells in various tissues. With a transmembrane region consisting of seven α-helical segments, Lgr5 plays a pivotal role in maintaining the delicate balance between stem cell self-renewal and differentiation. This regulatory function is primarily executed through the potentiation of the Wnt/β-catenin signaling pathway upon binding with its ligands, R-spondins. This article provides a comprehensive review on molecular mechanisms by which Lgr5 modulates stem cell behavior and its indispensable role in the formation of digestive system organoids, including intestine, liver, and pancreas. We first elucidate the synergistic interplay between Lgr5-mediated Wnt signaling and other crucial pathways such as BMP, Notch, and EGF, which collectively create a biomimetic “niche” for organoid development in vitro. This Lgr5-mediated self-organization serves as the biological foundation for constructing three-dimensional (3D) organoids, as 3D cell clusters derive from stem cells with structural and functional characteristics that closely mimic native organs. Compared to traditional 2D cell cultures, organoids offer a superior model for studying tissue physiology and complex cell-cell interactions. Furthermore, this review highlights the diverse applications of digestive system organoids in biomedical research. In disease modeling, we discuss how these platforms simulate the pathological progression of colorectal cancer, non-alcoholic fatty liver disease, and hereditary metabolic disorders through CRISPR-Cas9 gene editing and environmental induction. In the field of regenerative medicine, the potential of organoids as transplantable units for repairing intestinal mucosal damage and reconstructing bile duct structures is explored. Despite the significant advancements, critical challenges remain in the current development of organoid technology. We identify several major limitations. First, organoids are highly dependent on animal-derived basement membrane matrix, which has poorly defined components. Second, current models lack functional vascularization. Third, they lack an integrated immune microenvironment. These limitations restrict the translational potential of organoid technology. To address these challenges, we propose future research directions, emphasizing the integration of microfluidic “organ-on-a-chip” systems, synthetic bio-scaffolds, and multi-lineage co-culture techniques. These innovations aim for more complexity and standardization in organoid models, providing a more robust theoretical and technical foundation for personalized medicine and drug discovery for digestive diseases.关键词：Lgr5;organoids;Wnt/β-catenin;Regulation of Stem Cell Function;Disease modeling39|3|0更新时间：2026-03-07
- 摘要：This paper systematically investigates the technological breakthroughs and ethical issues of synthetic biology in the context of medical diagnosis and treatment. With the rapid evolution of enabling technologies such as gene editing, DNA synthesis and assembly, regulatory element design, and metabolic engineering, synthetic biology has been transformed from theoretical frameworks to practical clinical applications. These advances have unlocked new possibilities for precision therapy, particularly in treating genetic and complex diseases. However, these innovations also introduce profound ethical dilemmas that necessitate policy-making and practice as well. The study conceptualizes the ethical challenges of therapeutic synthetic biology from three dimensions: practical, sociopolitical, and categoriality. In the practical dimension, the primary concerns involve biosafety, off-target effect and clinical risk. The sociopolitical dimension explores biosecurity, demographics of biotechnologies, and global health equity, emphasizing the structural inequalities in access to advanced therapies. The categorical dimension raises fundamental concerns about genomic integrity, intergenerational ethics, and human dignity—issues that underscore the moral limits of applying biotechnology to human life. To address these complex issues, the paper proposes an ethical governance framework grounded in human-centered principles, risk minimization, sustainable development and systematic govermance model. It highlights the importance of systematized risk management, participatory governance. Furthermore, it examines comparative international governance models from Europe, the United States, and China, reflecting how differing political and cultural contexts shape regulatory responses to synthetic biology. Ultimately, the paper argues that responsible innovation in medical synthetic biology must balance technological progress with ethical stewardship, emphasize the continuous improvement of ethical supervision, and ensure that the direction of technological development is consistent with the common values of humanity through multi-disciplinary collaboration and public involvement. This integrated approach ensures that synthetic biology not only advances the frontiers of medicine, but also aligns with shared human values, social justice, and ecological safety. By doing so, it contributes to the sustainable and equitable application of biotechnology in enhancing human health.关键词：synthetic biology;gene editing;Medical Diagnosis and Treatment;ethical issue;biosafety19|2|0更新时间：2026-03-07
- 摘要：With the rapid rise of synthetic genes and engineered bacteria in disease diagnosis and treatment, they pose a growing risk of biosafety. We review the biosafety strategies based on synthetic biology, and especially highlight recent studies on biocontainments with diagnosis or therapeutic bacteria. There are several goals of controlling biocontainments. One is to reduce the escape of engineered bacteria by limiting them within biological barriers. The second is to prevent synthetic genes transferring from engineered bacteria into other organisms. Auxotrophies and kill-switch are widely applied in controlling the biocontainment of engineered bacteria. Auxotrophic organisms with essential genes knockout rely on key metabolites that are supplemented for survival. Kill-switches are inducible toxic gene circuits, such as suicide switches and toxin-antitoxin systems. Once engineered bacteria leave from human bodies, the toxic genes are switched on to kill them. Genetic separation and DNA breaking are useful strategies to keep synthetic genes from spreading into environmental organisms. Essential genes and genes of interest can be distributed into multiple vectors or chromosomes, and each vector or chromosome depends on the others for replications. DNA breaking technologies like CRISPR or other DNA nucleases are used to digest chromosome or plasmid inside engineered bacteria, which regulate host survival and synthetic gene transferring. The feeding of unusual metabolites or engineering specific genes into engineered bacteria could lead to the spreading failure of the biocontaminants. Several unnatural nucleic acids have been developed for replication and transcription, and much more unnatural amino acids are deployed for protein translation. One advantage of these unnatural systems is the orthogonality, which prevent synthetic genes from transferring to natural organisms. The chemically synthesized unnatural nucleic acids and amino acids are not present in environments, so the synthetic auxotrophies can overcome the cross-feeding limitation of natural auxotrophies. Biosafety systems with multiple-layered designs based on different synthetic biological principles have potentials to solve the challenges in the future.关键词：biocontaminants;auxotrophies;suicide genes;toxin-antitoxin;gene editing;unnatural nucleic acids;unnatural amino acids18|6|0更新时间：2026-03-07
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