SBIR Phase I: An Engineering Platform for Adaptive Medicines

SBIR 第一阶段：适应性药物工程平台

• 批准号: 1747250
• 负责人: Philip Lee
• 金额: $ 22.5万
• 依托单位: SENTI BIOSCIENCES, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1747250&HistoricalAwards=false
• 关键词: SBIR; Phase; Engineering; Platform; Adaptive

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a cell-based platform technology that can sense inflammatory sites and respond by producing anti-inflammatory factors to treat autoimmune diseases. There are more than 80 types of autoimmune disease with more than 23.5 million Americans affected. Autoimmune diseases are the number one cause of morbidity for women in the U.S., and one of the top 10 causes of death for women under 65 years old. The annual healthcare burden of these diseases is estimated at more than $100 billion in the U.S. alone. Current treatments for autoimmune diseases are effective for some patients, but a majority either do not respond or become refractory. Furthermore, standard drugs result in systemic immune suppression, which can cause severe and chronic side effects. Hence, there is substantial market need for anti-inflammatory drugs that can act locally at the site of inflammation, and deliver the "right dose at the right time" depending on the severity of the flare. If successful, the adaptive cell therapy platform being developed in this proposal will serve as the basis for a next-generation therapy to existing biologics.This SBIR Phase I project proposes to develop a cell-based technology that localizes to a site of inflammation, senses inflammatory signals, and triggers the release of anti-inflammatory agents. The substantial technical and clinical progress made in recent years in synthetic biology and cell therapies is enabling development of this type of product. The goal is to design and optimize synthetic gene circuits to program cells to locally sense inflammatory signals such as TNFalpha and release anti-TNF drugs. The plan is to introduce these circuits into adult stem cells that have been used safely in numerous clinical trials against autoimmune diseases and have a well-established commercial development path. The engineered cells will be tested in culture to show input/output response to different levels of TNFalpha, and then tested in mouse models of disease. If successful, lead candidates will be further developed in a Phase II application.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发一种基于细胞的平台技术，可以感知炎症部位，并通过产生抗炎因子来治疗自身免疫性疾病。有超过80种类型的自身免疫性疾病，超过2350万美国人受到影响。自身免疫性疾病是美国女性发病的头号原因，也是65岁以下女性的十大死因之一。据估计，仅在美国，这些疾病的年度医疗负担就超过1000亿美元。目前对自身免疫性疾病的治疗对一些患者有效，但大多数患者要么没有反应，要么变得难治。此外，标准药物导致全身免疫抑制，这可能导致严重和慢性副作用。因此，市场上对能够在炎症部位局部发挥作用，并根据发作的严重程度在“正确的时间给予正确的剂量”的抗炎药物有很大的需求。如果成功的话，该项目中开发的适应性细胞治疗平台将成为现有生物制剂的下一代治疗的基础。SBIR第一阶段项目提出开发一种基于细胞的技术，定位于炎症部位，感知炎症信号，并触发抗炎剂的释放。近年来在合成生物学和细胞疗法方面取得的重大技术和临床进展使这类产品的开发成为可能。其目标是设计和优化合成基因电路，以编程细胞局部感知炎症信号，如TNF α，并释放抗TNF药物。该计划是将这些回路引入成人干细胞中，这些干细胞已经安全地用于许多针对自身免疫性疾病的临床试验，并且具有完善的商业开发路径。工程细胞将在培养中进行测试，以显示对不同水平的TNF α的输入/输出响应，然后在疾病的小鼠模型中进行测试。如果成功，主要候选人将在第二阶段应用中进一步发展。