bims-livmat 2026-06-21 papers

Synth Syst Biotechnol. 2026 Dec;14 459-470

Engineered bacteria in disease diagnosis and therapy: A synthetic biology perspective.

Yan Shen, Si-Ming Lu, Long Yang, Yang Li, Yu Zhang, Li-Guo Liang.

Synthetic biology is an interdisciplinary field that integrates knowledge and techniques from modern biology and many other disciplines to design and construct novel biological systems or to modify existing life forms. Its core technologies include gene editing (e.g., CRISPR/Cas9), DNA assembly, in vivo directed evolution, and integration with artificial intelligence. The development of these technologies has greatly advanced the application of synthetic biology in medicine. In disease diagnosis, engineered bacteria have shown considerable promise. They can be designed to sense disease-specific signals and produce detectable reporter outputs, thereby establishing new paradigms for early diagnosis and real-time disease monitoring. For example, bacteria engineered via synthetic biology have been developed as "living sensors" to detect disease biomarkers. In therapeutic applications, synthetic biology offers a fresh perspective on using microorganisms to treat diseases. Researchers can design and construct microorganisms with tailored functions for targeted drug delivery, immunotherapy, and microbiome modulation. These applications not only improve the precision and efficacy of treatments but also offer innovative solutions to overcome the limitations of conventional therapeutic approaches. However, despite their considerable potential, the clinical translation of engineered bacteria still faces numerous challenges, such as ensuring stable in vivo colonization, controlling immunogenicity, standardizing large-scale production, and establishing robust regulatory and ethical frameworks. This review summarizes engineering strategies aimed at enhancing the safety and efficacy of bacterial therapies, with the goal of optimizing bacterial functions and expanding their potential in diagnostics and precision medicine.

Keywords: CRISPR-Cas systems; Disease diagnosis; Engineered bacteria; Microbial therapeutics; Synthetic biology

DOI: https://doi.org/10.1016/j.synbio.2026.04.028

Trends Biotechnol. 2026 Jun 15. pii: S0167-7799(26)00235-0. [Epub ahead of print]

Engineered photothermal-responsive bacterial platform for in vivo fluorescence imaging-guided photothermal/gene combined breast cancer therapy.

Jingyu Zhang, Bin Guo, Zhenlong Wang, Fan Zhang, Xiaorui Shi, Chong Hu, Zeping Yang, Yingli Shen, Fu Wang.

By leveraging the capacity of near-infrared light to penetrate deep tissue, we devised an engineered bacterial system for fluorescence imaging-guided photothermal/gene combined cancer therapy. By incorporating a thermosensitive plasmid carrying a payload of cytolysin A (ClyA) into the probiotic Escherichia coli Nissle 1917 (EcN) and incubating it with the photothermal agent indocyanine green (ICG)/Cremophor EL, we generated engineered bacteria capable of photothermal conversion. Upon irradiation with a near-infrared laser, ICG within the engineered bacterial cells converted them into localized heat above 42°C. This simultaneous photothermal therapy cleverly activated the expression of the therapeutic protein ClyA, resulting in the synergistic killing of tumor cells. Importantly, as a natural immune adjuvant, EcN enhanced the body's immune response. In addition, the engineered bacteria exhibited significant cytotoxic effects on tumor cells and suppressed tumor growth. Our study demonstrates a near-infrared laser-controlled bacterial platform that can be applied to precision cancer therapeutics.

Keywords: bacterial therapy; engineering bacteria; fluorescence imaging; immunotherapy; photothermal therapy

DOI: https://doi.org/10.1016/j.tibtech.2026.05.022

Future Microbiol. 2026 Jun 13. 1-16

Engineering Lactobacillus for therapeutic delivery and biosensing: lessons from niche adaptation.

Prateeti Pal, Subham Sarkar, Jenifer Rajak, Srinjoy Maitra, Hailah M Almohaimeed, Waheeb Sami Aggad, Amany I Almars, Arup Kumar Mitra, Daniel Ejim Uti, Bikram Dhara.

Lactobacillus species are renowned for their probiotic properties and niche adaptability, driven by unique genomic traits, stress-response mechanisms, and biofilm formation. This versatility makes them exceptional candidates for advanced biotechnological applications. Their biocompatibility and immunomodulatory effects allow them to serve as live biotherapeutic products. Through genetic engineering and encapsulation, Lactobacillus can be programmed to deliver recombinant proteins and vaccines, cytokines and anti-inflammatory molecules, targeted enzymes, and peptides. Beyond therapy, these bacteria can be engineered into biosensors to detect pathogens, toxins, and clinical biomarkers. By integrating CRISPR-Cas systems and reporter genes into whole‑cell or cell‑free platforms, they offer robust solutions for food safety, environmental monitoring, and diagnostics. While challenges in stability and regulation persist, advancements in synthetic biology are transforming Lactobacillusfrom a simple probiotic into a precise, multifunctional tool for improving global health and environmental oversight.

Keywords: Biosensor; CRISPR-Cas; Lactobacillus; microfluidics; niche adaptability; therapeutics

DOI: https://doi.org/10.1080/17460913.2026.2686558

Proc Natl Acad Sci U S A. 2026 Jun 30. 123(26): e2530456123

Mycoelectronics: Bioprinted living fungal bioelectronics for artificial sensation.

Yulu Cai, Hang Yuan, Caleb Ronders, Vittorio Mottini, Kalpana Singh, Liuxi Xing, Iha Singh, Denghao Fu, Kyla Zhao, Linux Heller, Khoi Nguyen, Bryce Waller, Tuo Wang, Gregory Bonito, Jinxing Li.

The intelligence of the human biological system is enabled by the highly distributed sensing receptors on soft skin that can distinguish various stimulations or environmental cues, thus establishing the fundamental logic of sensing and physiological regulation or response. To replicate biological perception, biohybrid systems integrating living organisms with electronics have been developed to sense environmental cues. However, current eukaryote-based biohybrids face slow growth, strict culture needs, and short lifespans, limiting real-world use. Here, we introduce fungi-based printable "Mycoelectronics" which are created by additive bioprinting of living fungal mycelium networks onto stretchable electronics, as a practical living thermoresponsive sensory platform. This mycoelectronics approach leverages fung's capabilities for rapid biological responsiveness, cultivability with exponential growth, stability and self-healing in ambient conditions, bioprintability for scalable manufacturing, and mechanical flexibility for seamless integration with soft electronics. We show that the thermal responsiveness of the fungal network arises from intrinsic cellular processes-specifically, heat-induced vacuole remodeling and fusion, which modulate ionic transport and thus the electrical conductivity of the mycelial cells and networks, enabling a rapid response. By bridging the gap between cell biology and soft electronics, the mycoelectronics device, with a living mycelial network, functions as a thermal sensation system with rapid response and intrinsic self-healing properties, autonomously restoring sensing capabilities after damage and establishing sensing pathways in hard-to-reach locations. Application demonstrations in environmental and agricultural monitoring and wearable sensing systems for humans and robots highlight the versatility of this living fungal sensor platform, suggesting promising opportunities in healthcare and the environment.

Keywords: biohybrids; biomanufacturing; engineered living materials

DOI: https://doi.org/10.1073/pnas.2530456123

Stem Cell Res Ther. 2026 Jun 17.

Interleukin-10-engineered mesenchymal stem/stromal cells exhibit robust immunomodulatory effects in vitro and in vivo.

Diego de Carvalho Carneiro, Cássio Santana Meira, Rosane Borges Dias, Vinícius Pinto Costa Rocha, Patrícia Kauanna Fonseca Damasceno, Josiane Dantas Viana Barbosa, Milena Botelho Pereira Soares.

INTRODUCTION: A dysregulated inflammatory response to infection can lead to sepsis, a leading cause of mortality worldwide, and effective anti-inflammatory therapies remain limited. Mesenchymal stem/stromal cells (MSCs) are attractive candidates as immunomodulatory agents. This study evaluated whether genetic modification of MSCs to express interleukin-10 (IL-10), a key anti-inflammatory cytokine, enhances their immunomodulatory effects.
METHODS: Bone marrow-derived MSCs from C57Bl/6 mice were genetically engineered by lentiviral transduction to express mouse IL-10 (MSC-IL-10). The immunomodulatory activity in vitro was assessed by co-cultures with macrophages stimulated with LPS and IFN-γ, as well as in Con A-stimulated splenocytes. BALB/c mice subjected to lipopolysaccharide (LPS)-induced endotoxemia were treated with vehicle, dexamethasone, wild-type MSCs (MSC-WT), or MSC-IL-10. Survival, plasma cytokines, leukocyte profiles, CD11b⁺ inflammatory cells, and organ histopathology and biodistribution were evaluated in vivo.
RESULTS: MSC-IL-10 maintained the mesenchymal phenotype and multipotent characteristics while exhibiting robust IL-10 expression. In in vitro assays, MSC-IL-10 significantly decreased the production of the cytokines TNF-α, IL-1β, IL-6, IL-12 or Nos2 expression by stimulated macrophages or splenocytes, demonstrating superior immunomodulatory effects compared to MSC-WT. In in vivo mice models, MSC-IL-10 significantly reduced systemic pro-inflammatory cytokines, restored circulating leukocyte counts, and attenuated CD11b⁺ (Mac-1 integrin) inflammatory cell recruitment, surpassing MSC-WT-treated groups. Importantly, MSC-IL-10 mitigated tissue damage mainly to lungs and exhibited biodistribution to liver, lungs and spleen in LPS-challenged mice.
CONCLUSIONS: These results support an enhanced immunomodulatory effect of IL-10-expressing MSCs as a promising cell-based therapeutic approach for sepsis and other inflammatory and immune mediated disorders.

Keywords: Endotoxemia; Gene and cell therapy; IL-10; Inflammation; Lentivirus; Sepsis

DOI: https://doi.org/10.1186/s13287-026-05093-3