SBIR Phase I: Development of a genomic targeting drug delivery platform

SBIR 第一阶段：基因组靶向药物递送平台的开发

• 批准号: 1914294
• 负责人: Sean Jeffries
• 金额: $ 22.5万
• 依托单位: DESIGN THERAPEUTICS, 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: 2019-07-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1914294&HistoricalAwards=false
• 关键词: SBIR; Phase; Development; genomic; targeting

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is a technology that enables the development of novel therapeutics to treat a range of serious genetic neurodegenerative diseases. The proposed drug delivery platform would help improve the understanding of the root cause of certain genetic neurodegenerative diseases. Further, new therapeutics to treat the root cause of severe neurogenerative disorders would have strong commercial potential. Currently, patients have limited treatment options and require significant and costly supportive care. New therapeutics would both improve the lives of patients and create value for insurance providers by reducing the need for costly care.This SBIR Phase I project proposes to demonstrate proof-of-concept for a genomic targeting drug-delivery platform. Unstable nucleotide repeats in the genome have been identified as the root cause of over 20 neurodegenerative conditions. These are debilitating disorders with high disease burden impacting millions of lives. Most nucleotide repeat expansion diseases are caused by a toxic gain-of-function mutation in a single allele. These diseases show dominant inheritance where most patients have a normal, unaffected copy. Silencing expression of the disease allele would address the root cause of the disease, completely halt progression of degenerative symptoms, and likely enable patients to regain lost function. The proposed effort seeks to develop a proof-of-concept allele-specific gene modulator that silences the mutant allele in myotonic dystrophy 1 (DMPK). Using this drug delivery platform, the objective is to synthesize molecules that would target transcriptional repressors specifically to the diseased DMPK allele. Using patient cells, the plan is to test for molecules that silence expression from the repeat containing diseased DMPK allele without impacting the healthy copy.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.

这项小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力是一项技术，它使新型治疗剂的发展能够治疗一系列严重的遗传神经退行性疾病。提出的药物输送平台将有助于提高对某些遗传神经退行性疾病的根本原因的理解。此外，治疗严重神经发生疾病的根本原因的新疗法将具有强大的商业潜力。目前，患者的治疗方案有限，需要大量且昂贵的支持护理。新的治疗剂既可以改善患者的生活，又可以通过减少对昂贵的护理的需求来为保险提供者创造价值。该SBIR I期项目提议为靶向药物分娩平台提供概念证明。基因组中不稳定的核苷酸重复序列已被确定为超过20个神经退行性条件的根本原因。这些正在使疾病具有高昂的疾病，影响了数百万的生命。大多数核苷酸重复膨胀疾病是由单个等位基因中的功能障碍突变引起的。这些疾病在大多数患者的副本正常，未受影响的副本中显示出主导的遗传。疾病等位基因的沉默表达将解决该疾病的根本原因，完全停止退化症状的进展，并可能使患者恢复功能降低。拟议的努力旨在开发一种概念验证等位基因特异性基因调节剂，该基因调节剂使肌营养不良1（DMPK）中的突变等位基因沉默。使用此药物输送平台，目的是合成将转录阻遏物专门针对患病DMPK等位基因的分子。使用患者细胞，该计划是测试分子，即从包含患病的DMPK等位基因的重复中表达沉默而不会影响健康副本。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力优点和更广泛影响的评估来支持的。