SBIR Phase II: Re-engineered skin bacteria as a novel topical drug delivery system

SBIR II 期：重新设计皮肤细菌作为新型局部给药系统

• 批准号: 1853071
• 负责人: Travis Whitfill
• 金额: $ 71.97万
• 依托单位: Azitra Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1853071&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Re; engineered

This SBIR Phase II project aims to develop a novel engineered microbiome as a potential therapeutic for a rare skin disease called Netherton syndrome. Netherton syndrome (NS) is a rare, severe skin disease with high mortality and few treatment options. This proposal aims to develop a new therapeutic for this disease, a microbe-based protein delivery system of LEKTI, the missing protein responsible for NS symptoms. At the end of this project, a candidate live biotherapeutic product candidate (LETKI-secreting strain of S. epidermidis) will be nominated and the Company will have sufficient data with which to proceed into formal preclinical studies and subsequent human testing. This proposed product will have the potential to address thousands of patients in the U.S., and the broader proof-of-principle of this microbe-based technology offers significant potential to treat millions of patients living with skin conditions. This offers significant advances in innovation in addition to broad commercial potential.This project aims to develop a novel therapeutic candidate composed of an engineered strain of S. epidermidis that secretes LEKTI protein to the skin for the treatment of Netherton syndrome (NS). NS is a rare but severe autosomal recessive disease that affects the skin, hair, and immune system. NS is caused by mutations in in the SPINK5 gene encoding the serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI), which contains 15 serine protease inhibitory domains. The goal of this Phase II project is to demonstrate a proof-of-concept therapeutic for NS: an engineered commensal microbe that delivers discrete domains of LETKI to the skin. The proposed Phase II research plan will establish critical criteria for nominating a potential live biotherapeutic product (LBP) candidate composed LEKTI-secreting S. epidermidis. This research will perform key activities in preclinical development of an LBP: identify an optimal sequence of LEKTI; develop analytical methods for detecting LEKTI secreted from an engineered strain of S. epidermidis; and develop analytical methods for measuring biodistribution and adsorption of LEKTI secreted by S. epidermidis in a human in vitro model.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.

这个SBIR二期项目旨在开发一种新的工程微生物组，作为一种罕见皮肤病内瑟顿综合征的潜在治疗方法。内瑟顿综合征（NS）是一种罕见的严重皮肤病，死亡率高，治疗选择少。该提案旨在开发一种新的治疗方法，即基于微生物的LEKTI蛋白递送系统，LEKTI是NS症状的缺失蛋白。在本项目结束时，将提名一种候选活生物治疗产品（表皮葡萄球菌的letki分泌菌株），公司将有足够的数据进行正式的临床前研究和随后的人体试验。这种拟议的产品将有可能解决美国数千名患者的问题，并且这种基于微生物的技术的更广泛的原理证明为治疗数百万患有皮肤病的患者提供了巨大的潜力。除了广泛的商业潜力外，这还提供了创新方面的重大进步。该项目旨在开发一种由表皮葡萄球菌工程菌株组成的新型候选治疗药物，该菌株可向皮肤分泌LEKTI蛋白，用于治疗内瑟顿综合征（NS）。NS是一种罕见但严重的常染色体隐性疾病，影响皮肤，头发和免疫系统。NS是由编码丝氨酸蛋白酶抑制剂淋巴上皮卡扎尔型相关抑制剂（LEKTI）的SPINK5基因突变引起的，该基因含有15个丝氨酸蛋白酶抑制结构域。该二期项目的目标是展示一种用于NS的概念验证疗法：一种工程共生微生物，可将LETKI的离散域传递到皮肤。拟议的II期研究计划将为提名由分泌lekti的表皮葡萄球菌组成的潜在活生物治疗产品（LBP）候选物建立关键标准。这项研究将在LBP的临床前开发中发挥关键作用：确定LEKTI的最佳序列；建立表皮葡萄球菌工程菌株分泌LEKTI的分析方法；建立测定表皮葡萄球菌分泌的LEKTI在人体外模型中的生物分布和吸附的分析方法。该奖项反映了美国国家科学基金会的法定使命，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。