I-Corps: Time-Dependent Protein Response Platform

I-Corps：时间依赖性蛋白质响应平台

• 批准号: 1917312
• 负责人: Rhonda Shrader
• 金额: $ 5万
• 依托单位: University of California-Berkeley
• 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 2020-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1917312&HistoricalAwards=false
• 关键词: Corps; Time; Dependent; Protein; Response

The broader impact/commercial potential of this I-Corps project is the development of novel therapeutics for the treatment of respiratory disease. For example, a significant percentage of pre-term babies are unable to produce lung surfactant. This biological material, which contains lipid and specialized proteins, significantly increases the ability of the lung to expand and contract. It also enhances the transfer of oxygen to blood. Insufficient levels of lung surfactant results in neonatal respiratory distress syndrome (NRDS), a condition that is fatal in a significant number of cases. The current standard of care is a purified extract obtained from pig lung. The purification process used to obtain this product is demanding, resulting in a final product that varies significantly in protein and lipid content. For this reason, there is significant interest in the development of novel synthetic lung surfactants. However, chemically-designed lung surfactants that have been developed to date are no longer used because of low biological potency. In addition to its therapeutic utility, a potent, concentrated lung surfactant may also be useful in treating babies with less severe forms of this disease and may be useful in the treatment of adult diseases such as adult respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disorder (COPD). This I-Corps project is to commercialize a scalable, fully active synthetic lung surfactant for use in the treatment of neonatal and adult respiratory disorders. The approach is unique since computational models of lung surfactants are being used to identify key structural features that are required for biological activity and manufacturability. The project's hypothesis is that this synthetic lung surfactant can be successfully commercialized at reasonable cost. In addition, we hypothesize that the knowledge gained can be leveraged to develop other biotherapeutics requring interaction between bioactive proteins and lipid. We will use the lean startup method to perform customer interviews that assess the commercial viability of a novel synthetic lung surfactant.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.

该I-Corps项目的更广泛的影响/商业潜力是开发用于治疗呼吸系统疾病的新型治疗剂。例如，很大一部分前婴儿无法产生肺表面活性剂。这种包含脂质和专业蛋白质的生物材料可显着提高肺部扩张和收缩的能力。 它还增强了氧气向血液的转移。 肺表面活性剂水平不足会导致新生儿呼吸窘迫综合征（NRDS），这种情况在大量病例中致命。 当前的护理标准是从猪肺中获得的纯化提取物。 用于获得该产品的纯化过程是要求的，导致最终产品在蛋白质和脂质含量上差异很大。 因此，对新型合成肺表面活性剂的发展具有重大兴趣。 但是，由于生物学效力低，迄今为止已开发的化学设计的肺表面活性剂不再使用。 除了其治疗效用外，有效的浓肺表面活性剂也可能有助于治疗这种疾病较少形式的婴儿，并且可能有助于治疗成人疾病（例如成人呼吸道遇险综合症（ARDS）和慢性阻塞性肺疾病）（COPD）。这个I-Corps项目是将可扩展的，完全活跃的合成肺表面活性剂商业化，用于治疗新生儿和成人呼吸系统疾病。 该方法是独一无二的，因为使用肺表面活性剂的计算模型来识别生物活动和生产性所需的关键结构特征。 该项目的假设是，这种合成的肺表面活性剂可以以合理的成本成功商业化。 此外，我们假设可以利用获得的知识来发展生物活性蛋白与脂质之间的其他生物治疗剂。 我们将使用精益启动方法进行客户访谈，以评估新型合成肺表面活性剂的商业生存能力。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响评估标准，认为值得通过评估值得支持。