ArticleJournal of controlled release : official journal of the Controlled Release Society2025
Programmable chronogenetic gene circuits for self-regulated circadian delivery of biologic drugs.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Harnessing spatiotemporal melatonin delivery from engineered platforms for targeted microenvironment remodeling in peripheral neuropathy.Materials today. Bio · 2026Review
- Circadian engineering of in vivo CAR T cell therapy for precision oncology.NPJ precision oncology · 2026Review
- Identification of SNCA and DRD2 as key genes linking parkinson's disease and circadian rhythm through bioinformatics analysis.Scientific reports · 2025Article
- Dual-responsive synthetic gene circuit for dynamic biologic drug delivery via inflammatory and circadian signaling pathways.Journal of biological engineering · 2025Review
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7 authors.
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Abstract
Cells of the body rely on the circadian clock to orchestrate daily changes in physiology that impact both homeostatic and pathological conditions, such as the inflammatory autoimmune disease rheumatoid arthritis (RA). In RA, high levels of proinflammatory cytokines peak early in the morning hours, reflected by daily changes in joint stiffness. Chronotherapy (or circadian medicine) seeks to delivery drugs at optimal times to maximize their efficacy. However, chronotherapy remains a largely unexplored approach for disease modifying, antirheumatic treatment, particularly for cell-based therapies. In this study, we developed autonomous chronogenetic gene circuits that produce the biologic drug interleukin-1 receptor antagonist (IL-1Ra) with desired phase and amplitude. We compared expression of IL-1Ra from circuits that contained different circadian promoter elements (E'-boxes, D-boxes, or RREs) and their ability to respond to inflammatory challenges in murine pre-differentiated induced pluripotent stem cells (PDiPSC) or engineered cartilage pellets. We confirmed that each circuit reliably peaked at a distinct circadian time over multiple days. Engineered cells generated significant amounts of IL-1Ra on a circadian basis, which protected them from circadian dysregulation and inflammatory damage. These programmable chronogenetic circuits have the potential to align with an individual's circadian rhythm for optimized, self-regulated daily drug delivery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.