Curated Optogenetic Publication Database

Abstract: Engineered yeast-living drugs offer significant potential for oral protein therapy but remain limited by poor intestinal retention and lack of precise spatiotemporal control over therapeutic delivery. Here, we developed an ingestible hydrogel-encapsulated optogenetic yeast system controlled by a wearable electronic device for programmable interleukin-10 (IL-10) delivery in inflammatory bowel disease (IBD). We engineered Pichia pastoris with an EL222-based blue-light-inducible circuit achieving rapid, stringent IL-10 secretion (50% saturated concentration within just 1 h upon induction). The yeast was encapsulated in a photo-crosslinkable HAMA hydrogel that was gelated within 60 s upon blue-light exposure, exhibiting robust mechanical stability and tissue adhesion. A lightweight (2.27 g) wearable Bluetooth-controlled electronic device delivered targeted blue light transdermally, enabling simultaneous in situ hydrogel crosslinking and optogenetic activation in yeast cells. This system significantly extended the time yeast stays in the mouse gut, with reporter gene expression lasting over 5 h, while the unencapsulated control group lasted less than 2 h. In DSS-induced colitis mice, our strategy reduced proinflammatory cytokines (IL-1β, IL-6, and TNF-α) by >60%, restored intestinal barrier integrity, and normalized gut microbiota diversity to near-healthy levels, which performed significantly better than in other groups. This integrated "extracorporeal instruction-intracorporeal response" paradigm establishes a digitally programmable platform for precision live biotherapeutics. However, limited blue-light tissue penetration remains a key constraint; future work should focus on near-infrared photosensitive systems, programmable-degradation hydrogels, and wireless closed‑loop feedback to advance clinical translation.

Abstract: Engineered bacteria-based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria-mediated photodynamic therapy (PDT)-immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria-based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT-immunotherapy. The biosynthetic pathway of 5-aminolevulinic acid (5-ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light-controllable releasement of anti-programmed cell death-ligand 1 nanobodies (anti-PD-L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria-based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT-immunotherapy.