Presentation Information
[P04-453]Engineering Escherichia coli Nissle 1917 for the Treatment of Hyperuricemia by Expressing Genome-Mined High-Activity Uricase
○YooHo SHIN1, Jina Yang2, HoJoon Kim1, SangWoo Seo1 (1. Seoul Nat. Univ. (Korea), 2. Jeju Nat. Univ. (Korea))
Keywords:
Hyperuricemia,Uricase,Nissle,Genome-mining
Hyperuricemia, defined as abnormally high levels of uric acid in the blood, is closely associated with metabolic and cardiovascular disorders, particularly gout. The primary cause of hyperuricemia is the absence of functional uricase in humans, which leads to uric acid accumulation when renal or intestinal excretion is insufficient.
Xanthine oxidase inhibitors are the conventional treatment for gout, but they can cause serious side effects. Uricase-based treatments have emerged as an alternative, but current uricase drugs are administered intravenously. This route of administration carries the risk of provoking strong immune responses. Therefore, the development of orally deliverable uricase drugs is highly desirable as a safer alternative.
Escherichia coli Nissle 1917, a strain originally isolated from human feces, is widely recognized as a probiotic strain and is used in commercially available products. Its GRAS (Generally Recognized As Safe) status and compatibility with the gut microbiome make it a promising chassis for the development of living therapeutics.
In this study, we aim to identify high-activity uricase candidates through genome mining and to engineer E. coli Nissle 1917 to express them. We anticipate that oral administration of the engineered strain will effectively reduce serum uric acid levels and alleviate hyperuricemia in a murine model.
Xanthine oxidase inhibitors are the conventional treatment for gout, but they can cause serious side effects. Uricase-based treatments have emerged as an alternative, but current uricase drugs are administered intravenously. This route of administration carries the risk of provoking strong immune responses. Therefore, the development of orally deliverable uricase drugs is highly desirable as a safer alternative.
Escherichia coli Nissle 1917, a strain originally isolated from human feces, is widely recognized as a probiotic strain and is used in commercially available products. Its GRAS (Generally Recognized As Safe) status and compatibility with the gut microbiome make it a promising chassis for the development of living therapeutics.
In this study, we aim to identify high-activity uricase candidates through genome mining and to engineer E. coli Nissle 1917 to express them. We anticipate that oral administration of the engineered strain will effectively reduce serum uric acid levels and alleviate hyperuricemia in a murine model.
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