I-Corps: Time-Dependent Protein Response Platform

I-Corps项目更广泛的影响/商业潜力是开发治疗呼吸系统疾病的新疗法。例如，相当大比例的早产儿无法产生肺表面活性物质。这种含有脂质和特殊蛋白质的生物材料显著增强了肺的扩张和收缩能力。它还能加强氧气向血液的转移。肺表面活性物质水平不足会导致新生儿呼吸窘迫综合征(NRDS)，这种情况在相当多的病例中是致命的。目前的护理标准是从猪肺中提取的纯化提取物。用于获得这种产品的纯化过程要求很高，导致最终产品的蛋白质和脂肪含量差异很大。因此，开发新型的合成肺表面活性物质引起了人们的极大兴趣。然而，到目前为止已经开发出来的化学设计的肺表面活性物质由于生物效力低而不再使用。除了它的治疗作用，一种有效的、浓缩的肺表面活性物质也可能对治疗这种疾病的较轻形式的婴儿有用，并可能对成人疾病的治疗有用，如成人呼吸窘迫综合征(ARDS)和慢性阻塞性肺疾病(COPD)。这个i-Corps项目是为了将一种可扩展的、完全活性的合成肺表面活性物质商业化，用于治疗新生儿和成人呼吸系统疾病。这种方法是独一无二的，因为肺表面活性物质的计算模型被用来确定生物活性和可制造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物质可以以合理的成本成功商业化。此外，我们假设所获得的知识可以被用来开发其他需要生物活性蛋白和脂质之间相互作用的生物疗法。我们将使用精益启动方法进行客户访谈，以评估一种新型合成肺表面活性剂的商业可行性。该奖项反映了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 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.