
With the rapid development of frontier biomedical technologies, multi-omics integration, single-cell and spatial omics, artificial intelligence, and emerging translational technologies are reshaping disease research. These technologies have not only deepened our understanding of disease heterogeneity, microenvironmental interactions, and molecular regulatory networks, but also promoted the transition of disease research from single-level investigation toward systematic analysis, functional validation, and precision intervention. This review summarizes the advances that have been made over the past five years in the areas of multi-omics integration, single-cell and spatial omics, and artificial intelligence, and introduces representative translational technologies, including nanobiosensors, gene delivery systems, organs-on-chips, and recombinant live biotherapeutic products. Particular attention is given to the common challenges associated with cross-scale integration, the observation of dynamic processes, causal inference, standardization, and clinical validation. Future directions, including multimodal integration, interpretable modeling, functional experiments, and prospective validation, are further discussed to provide a reference for advancing frontier biomedical technologies from high-dimensional observation to mechanistic investigation and clinical application.
Cytokines are a class of protein factors that regulate immune homeostasis, inflammatory responses, cell proliferation and differentiation, and cell death. In China, the drug research and development in this field has formed a unique “Chinese paradigm”. This article systematically reviews the innovation and development process of Chinese cytokine drugs, represented by cell growth factors, from the technological breakthroughs in the 1980s to the collaborative transformation of industry-university-research in the 1990s, and to the full process of long-acting, precise, and high-quality development in the 21st century. In terms of the expression and key technologies of industrialization, this paper expounds on the technical systems and bottleneck-solving strategies of the three mainstream expression systems currently in use, as well as the breakthroughs in protein engineering modifications and long-acting technologies such as site-directed mutagenesis, PEG modification, and Fc fusion. At the industrial and product level, it summarizes the category layout and clinical indications of representative mainstream cytokine drugs that have been launched domestically. It also analyzes the product iteration paths from ordinary recombinant proteins to compound preparations and carrier sustained-release systems. It also focuses on the core weaknesses of domestic research and development in aspects such as formulation stability, targeted delivery, long-acting technologies, and industry homogenization competition. It then discusses prospective innovative directions, such as AI-driven precise molecular modification, intelligent sustained-release delivery carriers, and synthetic biology-driven green manufacturing. This article provides a systematic reference for the continuous innovation and high-quality development of recombinant cytokine drug research and development in China.
Particle-based vaccine delivery systems play an important role in various novel vaccine formulations, owing to their diverse material properties, ease of surface modification, and multifunctional integration. They significantly enhance immune protection through mechanisms such as antigen protection, antigen depot formation, cell recruitment, and targeted delivery. To promote the rational design of particle-based vaccine delivery systems, this article reviews recent progress in terms of the regulatory mechanisms of particles on immune responses, strategies for antigen targeting, and design of release profiles. The emphasis is on the effects of the physicochemical properties of particles, such as particle size, which determines lymph node accumulation efficiency and cellular uptake pathways, and surface charge, which influences antigen cellular uptake and lysosomal escape. Recent studies have also revealed that particle stiffness affects the mechanisms of immune action. Soft particles and deformable Pickering emulsions can increase the contact area between cells and particles through stress-induced deformation, thereby promoting cellular antigen uptake. In terms of targeted delivery, the article systematically elaborates on design strategies for hierarchical targeting at the organ, cellular, and subcellular levels. In addition, pulsatile-release particulate formulations can mimic the release profile of multiple vaccinations with a single injection, thereby reducing immunization costs and improving vaccination compliance. However, the current design of particle-based vaccine delivery systems still relies predominantly on prior empirical guidance and extensive trial and error. The introduction of artificial intelligence-assisted design is expected to overcome this bottleneck, accelerating the construction of novel delivery systems and enabling precise design of formulations for specific application scenarios, such as delivery systems suitable for mucosal immunity or for populations with low immune responsiveness. Meanwhile, combined efforts in scalable manufacturing, quality control, and regulatory science are expected to promtoe further research on particle-based delivery systems and provide solid support for the development of next-generation vaccines.
Microbial cell factories serve as core platforms for synthetic biology-driven biomanufacturing. However, incompatibilities between artificial metabolic pathways and chassis cells, which can occur at multiple levels, including genetic maintenance, expression resources, metabolic networks, reaction microenvironments, and bioprocess conditions, often result in phenotypic instability and reduced performance during scale-up. This review takes the whole life cycle of cell factory development, encompassing design, construction, optimization, and scale-up as its framework for analyzing compatibility issues across multiple cellular and process scales. The causes of incompatibility at different levels are summarized systematically, and the causal relationships and feedback interactions among these levels are discussed further. Traditional metabolic engineering strategies and emerging digital technologies for addressing compatibility challenges are reviewed, with emphasis on their mechanisms and optimization effects. Moreover, the key challenges and future prospects related to the scale-up of bioprocesses using microbial chassis are discussed. The concept of compatibility engineering for microbial cell factories is proposed, providing a systematic optimization framework for enabling the design, development, and industrial application of robust cell factories throughout their entire life cycle.
Halophilic microorganisms, particularly Halomonas species, have become representative chassis for next-generation industrial biotechnology (NGIB) owing to their ability to grow rapidly under high-salinity and high-pH conditions, as well as their natural resistance to contamination. Using the Halomonas chassis as a central thread and beginning with strain isolation from salt lakes in Xinjiang, this review systematically examines the development trajectory, technical bottlenecks, and industrial validation of high-salt fermentation technology systems. It then reviews methodological advances in marine microbial bioprospecting and the potential of genetic resources across the environmental gradient from salt lake to seawater to the deep sea. On this basis, AI-driven structural prediction of secondary metabolites is introduced, demonstrating a pathway for unlocking the “chemical dark matter” of marine microorganisms. Finally, this paper proposes that PhaBuilder’s established 10 000-ton-scale, high-salt fermentation production line not only solves the challenge of manufacturing PHA at a low cost, but also provides an ideal land-based infrastructure for translating deep-sea genetic resources into industrial applications. Within the broader framework of biomanufacturing, the value of marine halophilic microbial resources has expanded beyond the production of bulk chemicals to include intellectual property-intensive fields such as novel drugs, gene-editing tools, and functional proteins. This paper aims to offer a framework-level perspective of the entire marine biomanufacturing chain, from resource discovery to industrial implementation.
The field of biomanufacturing requires more efficient screening of enzyme molecules, engineered strains, functional cells, and synthetic biology elements. However, the traditional agar plates, microplates, and flow cytometric sorting are limited in terms of throughput, reagent consumption, detection of extracellular products, and genotype-phenotype linkage. Droplet microfluidics can encapsulate single cells or reaction units within microreactors that range from the picoliter to the nanoliter scale. This process enables the cultivation, detection, and sorting of cells in independent microenvironments, thereby providing an important platform for large-scale library screening. This review begins with the requirements of screening tasks and summarizes the design principles of droplet-based high-throughput screening platforms. It compares major droplet microreactors, and discusses strategies for acquiring and analyzing direct phenotypic signals, fluorescence-labeled signals, and label-free molecular phenotypes. It reviews droplet sorting, target recovery, system integration, and commercial devices. Then, it discusses future challenges and opportunities involving signal adaptation, sorting accuracy, artificial intelligence, and multimodal detection. Droplet microfluidic high-throughput screening platforms will be important for enzyme engineering, modifying cell factories, screening synthetic biology elements, optimizing cell-free systems, discovering antibodies, and evaluating organoid-based drugs.
As the population grows and resources become more limited, microbial protein is emerging as a promising alternative source of protein. However, existing reviews have overlooked the impact of its microscopic morphological and structural traits on processing adaptability and nutrition, focusing instead on macro aspects. This review covers the morphological, structural, and compositional diversity of microbial proteins, including those from yeast, fungi, bacteria, and microalgae (cell wall properties and spatial organization). We discuss how these traits determine thermal textural remodeling and how structural integrity controls digestion kinetics from the oral stage to the colonic stage. We also summarize structural regulation strategies via strain selection, synthetic biology-based modifications, and food processing technologies. Ultimately, we link the structure of microbial proteins to their functional performance, such as food processing and digestive characteristics, in order to guide the rational design of microbial foods that have the desired sensory and health attributes.
Glycans, as the “third life information chain” after nucleic acids and proteins, play essential roles in cell recognition, signal transduction, immune regulation, pathogen infection, and tumor metastasis. Over the past three decades, glycoscience and glycoengineering in China have evolved from foundational research to a comprehensive technological system. This review systematically examines the evolution of international glycoscience over the past 50 years and the developmental trajectory of China’s glycoengineering over the past 30 years. It emphasizes the current status and future trends in glycomics, glyco drugs and glycoconjugate vaccines, green biomanufacturing of functional carbohydrates, and emerging interdisciplinary fields, such as AI driven glycoanalysis and synthetic biology. Based on the China’s Glycoscience and Glycoengineering Technology Roadmap (2026-2035), four strategic directions have been proposed: intelligent glycan synthesis and analytical technologies, decoding the glycocode, precision manufacturing of glyco products, and glycomedicine for precision diagnostics and therapy. By 2035, China aims to achieve systemic breakthroughs in these areas, transitioning from a follower to a global leader in glycoscience. This roadmap serves as a strategic reference for advancing the high quality development of glycoengineering and capturing the global lead in glycoscience.
Salt stress is one of the primary abiotic stresses that constrain stable crop yields worldwide. Recent research has shifted from conventional damage observation to continuous monitoring of stress onset, injury severity, and plant recovery potential. Over the past decade, there have been rapid advances in phenomics, which have led to the development of high-throughput phenotyping platforms with integrated workflows that combine image acquisition, automated extraction, and statistical modeling. These non-destructive, continuous approaches enable researchers to capture digital traits that describe plant architecture, such as plant height and leaf angle, as well as spectral indices that reflect internal physiological status for population-scale comparative analysis. Recent studies on crop salt stress demonstrate that high-throughput phenomics facilitates earlier detection of stress responses and enhances the screening efficiency of stress-tolerant germplasm. Furthermore, this approach allows for the interpretation of morphological and physiological changes along the same timeline, laying the foundation for the subsequent joint analysis of plant genetic and phenotypic data. Currently, the capability of phenotypic data collection far exceeds that of data integration and predictive modeling. Moreover, the lack of standardized phenomic databases aligned with genomic databases leaves the potential of multidimensional phenotypic data largely underutilized. Consequently, there is an imperative need to systematically incorporate high-throughput phenomics into salt tolerance evaluation systems and to develop a standardized prediction framework that balances efficiency and precision. This will allow for the translation of identified salt-tolerance genes into practical field-ready breeding outcomes.
Neoproteins are protein products that are produced at scale through biomanufacturing systems, in contrast to conventional agricultural cultivation and livestock production. Their essence does not lie in simply substituting traditional protein sources; rather, it lies in a paradigm shift that transforms the source of supply, physiological value, and consumer perception simultaneously. The three defining attributes of neoproteins-“new sources, new functions, and new experiences”-are indispensable, because the development of neoproteins is grounded in the real needs of consumers, both at the starting point and the ultimate goal. Following this logic, this article reviews the underlying trajectory of industrial evolution, analyzes the practical barriers to translating research advances into industrial development, and proposes a strategic pathway centered on consumer needs and on building a coordinated, system-wide industrial ecosystem across the entire value chain. It aims to provide forward-looking insights for stakeholders in research, industry, policymaking, and investment.
Interferons are core, multifunctional cytokines of the host innate immune system that have broad-spectrum antiviral, anti-tumor and immunomodulatory effects. In 1978, the research team led by Academician Hou Yunde induced interferon α1b from human umbilical cord whole blood of Chinese donors via viral stimulation, followed by gene cloning to obtain recombinant human interferon α1b. As the world’s first interferon subtype derived from the yellow race, it was approved as China’s first Class 1 innovative genetically engineered drug with fully independent intellectual property rights. This paper provides a systematic review of its development journey over the past 50 years. In the 1980s, original breakthroughs were achieved in gene source innovation, and the research theory of population-adapted cytokine drugs was pioneered. In the 1990s, bottlenecks in expression and formulation industrialization were overcome, a dedicated quality control system was established, large-scale production and multi-indication layout were realized, and domestic substitution of interferons was completed. During the first decade of the 21st century, in-depth research was conducted in the field of chronic hepatitis, resulting in a wealth of evidence-based clinical data. During the second decade, innovative nebulized inhalation formulations expanded the drug’s therapeutic applications to include pediatric respiratory viral infections, and the drug was subsequently recommended by multiple clinical guidelines and expert consensuses. Over the past decade, it has served as a reserve drug for the prevention and control of the national public health emergency of the novel Coronavirus (SARS-CoV-2), while groundbreaking progress has been made in combined immunotherapy for malignant melanoma and other malignancies. Recombinant human interferon α1b fully witnesses the transformation of China’s biopharmaceutical industry from imitation to original, independent innovation. Its full-chain, independent intellectual property rights, as well as the superior safety and efficacy resulting from population adaptation, set a benchmark for the research and development (R&D) and industrial transformation of domestic recombinant protein drugs. It also continuously provides clinical support for the prevention and control of emerging infectious diseases, as well as comprehensive tumor treatment.
The policy of synthetic biology did not emerge only after the field acquired a distinct disciplinary identity. It evolved from the longer institutional histories of recombinant DNA governance, genetic engineering regulation, bioeconomy strategies, and research organization. Existing studies often arrange policy documents chronologically, yet they pay insufficient attention to how different instruments combine to support innovation, industrial translation, risk regulation, and organizational coordination. This study compares the United States, the United Kingdom, Germany, France, Australia, Japan, and China. It applies qualitative policy document analysis, structured and focused comparisons, and process tracing to examine laws, strategies, research programs, funding measures, guidelines, advisory reports, roadmaps, and coordination mechanisms issued before December 31, 2025. Although the seven national pathways differ from one another, they can be grouped into three types for comparison: existing-institution adaptation, strategic coordination, and national mission organization. A country may have features of more than one type. A policy change is not a simple, linear transition. Technological advances, commercialization needs, and competitive or security pressures only affect policy after being translated through institutional channels, such as expert assessment, legal authorization, executive coordination, and program management. At the global level, the prohibition of biological weapons, governance of biodiversity, benefit-sharing, oversight of dual use, screening of nucleic acids, and management of biorisk constitute a multilayered but fragmented system. The priority of science and technology policy for synthetic biology is not to replicate a single national model, but rather to develop a policy mix appropriate to each institution that integrates innovation support, industrial translation, risk regulation, and organizational coordination.
