SBIR Phase I: Optimizing Assembly of Bispecific Aptamer Therapeutics

SBIR 第一阶段：优化双特异性适体疗法的组装

• 批准号: 2127185
• 负责人: Douglas Gooding
• 金额: $ 25.6万
• 依托单位: DRIVE THERAPEUTICS, L.L.C.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2127185&HistoricalAwards=false
• 关键词: SBIR; Phase; Optimizing; Assembly; Bispecific

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to reduce the impact of preventable vision loss caused by retinal diseases such as the wet form of advanced macular degeneration (wAMD) and diabetic macular edema (DME). Vision loss has a significant impact on the lives of those who experience it as well as on society as a whole. The retinal therapeutics market was $13 B in 2018 and is projected to grow to $28B in 2025. The proposed project develops a new technology to address multiple aspects of eye disease, which is expected to improve clinical outcomes at reduced cost. This Small Business Innovation Research (SBIR) Phase I project will identify the best approach to combining anti-VEGF and anti-IL8 aptamers to generate a bispecific aptamer. Two different approaches will be evaluated: 1) direct chemical synthesis, in which the individual aptamer components are used to form a bispecific aptamer synthesized as a single compound, and 2) assembly by hybridization, in which individual aptamer components are synthesized separately with complementary extensions subsequently used for assembly. This project will assess the effect of linker identity and length on function, as well as the inhibitory activity, which will be compared with that of the individual aptamer components. The best performing bispecific aptamers will be PEGylated using at least two different PEG variants, and further evaluated. The biophysical properties of the PEGylated compounds will be assessed. These properties are key to establishing parameters for bispecific aptamer formulation and predicting intravitreal half-life. The best performing PEGylated bispecific aptamer function will be evaluated in vivo, to confirm its ability to engage its targets in an established animal model of retinal disease.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.

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是减少由视网膜疾病（如湿型晚期黄斑变性（wAMD）和糖尿病性黄斑水肿（DME））引起的可预防的视力丧失的影响。视力丧失对患者的生活以及整个社会都有重大影响。视网膜治疗市场在2018年为130亿美元，预计到2025年将增长到280亿美元。拟议的项目开发了一种新技术来解决眼病的多个方面，预计将以更低的成本改善临床结果。这个小型企业创新研究（SBIR）一期项目将确定结合抗vegf和抗il - 8适配体产生双特异性适配体的最佳方法。将评估两种不同的方法：1)直接化学合成，其中单个适体成分被用来形成作为单一化合物合成的双特异性适体；2)杂交组装，其中单个适体成分被单独合成，然后使用互补延伸进行组装。该项目将评估连接体身份和长度对功能的影响，以及抑制活性，并将其与单个适体成分进行比较。最好的双特异性适配体将使用至少两种不同的PEG变体进行聚乙二醇化，并进一步评估。聚乙二醇化化合物的生物物理性质将被评估。这些性质是建立双特异性适配体配方参数和预测玻璃体内半衰期的关键。将在体内评估表现最佳的聚乙二醇化双特异性适配体功能，以确认其在已建立的视网膜疾病动物模型中参与其靶标的能力。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。