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.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是一种技术，能够开发新的治疗方法来治疗一系列严重的遗传性神经退行性疾病。拟议的药物输送平台将有助于提高对某些遗传性神经退行性疾病根本原因的理解。此外，治疗严重神经变性疾病的根本原因的新疗法将具有强大的商业潜力。目前，患者的治疗选择有限，需要大量昂贵的支持性护理。新的治疗方法将改善患者的生活，并通过减少对昂贵护理的需求为保险提供商创造价值。SBIR第一阶段项目旨在展示基因组靶向药物输送平台的概念验证。基因组中不稳定的核苷酸重复序列已被确定为20多种神经退行性疾病的根本原因。这些是使人衰弱的疾病，具有影响数百万人生命的高疾病负担。大多数核苷酸重复扩增疾病是由单个等位基因中的毒性功能获得性突变引起的。这些疾病显示显性遗传，大多数患者具有正常的未受影响的副本。沉默疾病等位基因的表达将解决疾病的根本原因，完全停止退行性症状的进展，并可能使患者恢复失去的功能。该研究旨在开发一种概念验证等位基因特异性基因调节剂，使强直性肌营养不良1（DMPK）中的突变等位基因沉默。使用这种药物递送平台，目标是合成将特异性靶向患病DMPK等位基因的转录抑制因子的分子。利用患者细胞，该计划是测试沉默表达的分子，从重复含有患病DMPK等位基因，而不影响健康的副本。这个奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的智力价值和更广泛的影响审查标准。