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 II期项目旨在开发一种新型的工程微生物组，以作为一种称为Netherton综合征的稀有皮肤病的潜在治疗方法。 Netherton综合征（NS）是一种罕见的，严重的皮肤病，死亡率很高，治疗选择很少。该提案旨在为这种疾病开发一种新的治疗方法，该疾病是一种基于微生物的蛋白质递送系统，是负责NS症状的缺失蛋白质。在该项目结束时，将提名候选生物治疗产品候选（表皮链球菌分泌菌株），该公司将拥有足够的数据，可以进行正式的临床前研究和随后的人类测试。该提出的产品将有可能解决美国成千上万的患者，而这项基于微生物的技术的更广泛的原则证明为治疗数百万患有皮肤状况的患者提供了巨大的潜力。除了广泛的商业潜力外，这还提供了创新的重大进步。该项目旨在开发一种新型的治疗候选者，该候选者由s。pisterermidis的工程菌株组成，将Lekti蛋白分泌到皮肤上，以治疗Netherton综合征（NS）。 NS是一种罕见但严重的常染色体隐性疾病，会影响皮肤，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型Kazal-type相关抑制剂（LEKTI）中的Spink5基因突变引起的，该抑制剂（LEKTI）包含15个丝氨酸蛋白酶抑制域。该阶段项目的目的是证明NS的概念概念治疗：一种经过工程的共生微生物，将Letki的离散域传递给皮肤。拟议的第二阶段研究计划将建立提名潜在的生物治疗产品（LBP）候选列克蒂分泌S. epidermidis的关键标准。这项研究将在LBP的临床前开发中执行关键活动：确定Lekti的最佳序列；开发分析方法来检测从表皮链球菌的工程菌株中分泌的Lekti；并开发用于测量表皮链球菌在人类体外模型中分泌的Lekti生物分布和吸附的分析方法。该奖项反映了NSF的法定任务，并被认为值得通过基金会的知识分子优点和更广泛的影响标准通过评估来进行评估。