SBIR Phase I: Engineering probiotic yeast to treat hyperuricemia and gout

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力将是开发一种工程益生菌作为高尿酸血症和痛风的治疗方法。急性痛风发作会导致虚弱的疼痛和超敏反应，严重损害活动能力。随着时间的推移，关节损伤和畸形，慢性使用相关的疼痛，和毁容。虽然痛风可以通过降低尿酸水平的药物来治疗，但这些药物对许多患者来说有明显的缺点：它们的有效性有限，与严重的副作用有关，并且可能很昂贵。痛风患者的缺勤天数估计每年增加5天，每名患者的增量成本为3，000美元。美国920万痛风患者每年在痛风药物上花费超过13亿美元。此外，大约一半的人服用额外的补充剂。拟议项目将开发一种新型益生菌菌株来解决高尿酸血症。这个小企业创新研究（SBIR）第一阶段项目将使用工程益生菌来推进高尿酸血症治疗。所提出的治疗是基于这样的观察，即在肠道中酶促降解尿酸可降低血清尿酸水平，这与靶向循环系统、泌尿道或全身功能的常规治疗不同。该项目将使用遗传筛选来识别益生菌菌株来分解尿酸，对其进行工程改造以防止跨物种的基因流动，并避免抗生素耐药性转移到肠道微生物组。最后，我们将在高尿酸血症小鼠模型中确认安全性和有效性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will be the development of an engineered probiotic as an treatment for hyperuricemia and gout. Acute gout episodes cause debilitating pain and hypersensitivity, seriously impairing mobility. Over time, joint damage and deformity, chronic usage-related pain, and disfigurement follow. Although gout can be treated by drugs that lower uric acid levels, these drugs have significant drawbacks for many patients: they have limited effectiveness, are associated with serious side effects, and may be expensive. Gout patients experience an estimated increase of 5 absence days annually with an incremental cost of $3,000 per patient. The 9.2 million gout patients in the USA spend more than $1.3 billion per year on gout drugs. Moreover, roughly half take additional supplements. The proposed project will develop a novel probiotic strain to address hyperuricemia.This Small Business Innovation Research (SBIR) Phase I project will advance hyperuricemia treatment using an engineered probiotic. The proposed treatment is based on the observation that enzymatically degrading uric acid in the intestine reduces serum uric acid levels, unlike conventional treatments targeting the circulatory system, the urinary tract, or function systemically. This project will use genetic screening to identify a probiotic strain to break down uric acid, engineering it to prevent gene mobility across species and avoid transfer of antibiotic resistance to the intestinal microbiome. Finally, we will confirm safety and efficacy in a mouse model of hyperuricemia.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.