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: Engineering bacteria can achieve targeted and controllable cancer therapy using synthetic biology technology and the characteristics of tumor microenvironment. Besides, the accurate tumor diagnosis and visualization of the treatment process are also vital for bacterial therapy. In this paper, a light control engineered bacteria system based on upconversion nanoparticles (UCNP)-mediated time-resolved imaging (TRI) was constructed for colorectal cancer theranostic and therapy. UCNP with different luminous lifetimes were separately modified with the tumor targeting molecule (folic acid) or anaerobic bacteria (Nissle 1917, EcN) to realize the co-localization of tumor tissues, thus improving the diagnostic accuracy based on TRI. In addition, blue light was used to induce engineered bacteria (EcN-pDawn-φx174E/TRAIL) lysis and the release of tumor apoptosis-related inducing ligand (TRAIL), thus triggering tumor cell death. In vitro and in vivo results indicated that this system could achieve accurate tumor diagnosis and light-controlled cancer therapy. EcN-pDawn-φx174E/TRAIL with blue light irradiation could inhibit 53% of tumor growth in comparison to that without blue light irradiation (11.8%). We expect that this engineered bacteria system provides a new technology for intelligent bacterial therapy and the construction of cancer theranostics.

Abstract: Photodynamic therapy (PDT) and immunotherapy are considered promising methods for the treatment of tumors. However, these treatment systems are still suffering from shortcomings such as hypoxia, easy metastasis, and delayed immune response during PDT. Therefore, it is still challenging to establish a programmed and rapid response immune combination therapy platform. Here, we construct a two-step synergetic therapy platform for the treatment of primary tumors and distant tumors using upconversion nanoparticles (UCNPs) and engineered bacteria as therapeutic media. In the first step, erbium ion (Er3+)-doped UCNPs act as a photoswitcher to activate the photosensitizer ZnPc to produce 1O2 for primary tumor therapy. In the second step, thulium ion (Tm3+)-doped UCNPs can emit blue-violet light under the excitation of near-infrared (NIR) light to activate the engineered bacteria to produce interferon (INF-γ) and release them in the intestine, which can not only treat tumors directly but also act with PDT to regulate immune pathways to activate the immune system, resulting in a joint immunotherapy effect to inhibit the growth of distant tumors. As a new type of programmatic combination therapy, we have proved that this platform can jointly activate the body's immune system during PDT and immunization treatment and can effectively inhibit tumor metastasis.

Abstract: DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.