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

这一小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业潜力将是开发一种用于治疗高尿酸血症和痛风的工程益生菌。急性痛风发作会导致虚弱的疼痛和过敏，严重损害行动能力。随着时间的推移，关节损伤和畸形、慢性使用相关疼痛和毁容随之而来。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，与严重的副作用相关，而且可能很昂贵。据估计，痛风患者每年会增加5天的缺勤天数，每位患者的增量成本为3,000美元。美国920万痛风患者每年在痛风药物上的支出超过13亿美元。此外，大约一半的人服用额外的补充剂。拟议的项目将开发一种新的益生菌菌株来治疗高尿酸血症。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的治疗。拟议的治疗是基于观察到，在肠道中酶降解尿酸可以降低血清尿酸水平，而不是以循环系统、尿路或系统功能为目标的传统治疗方法。该项目将使用基因筛选来识别一种能够分解尿酸的益生菌菌株，对其进行改造，以防止基因跨物种迁移，并避免将抗生素耐药性转移到肠道微生物群。最后，我们将在高尿酸血症的小鼠模型中确认安全性和有效性。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.