Stimulated Raman Scattering to track the delivery of ASO and/or TPD into cells and tissues

受激拉曼散射可追踪 ASO 和/或 TPD 进入细胞和组织的情况

• 批准号: 2735134
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2735134
• 关键词: Stimulated; Raman; Scattering; track; delivery

Antisense oligonucleotides (ASOs) are a new therapeutic modality that have rapidly gained traction, with about 120 ASOs currently in clinical trials and 6 approved drugs on the market. ASOs are short, synthetic, chemically modified oligonucleotides that bind to the complementary sequence of the target RNA, inducing its degradation or alteration of splicing process. Despite their phenomenal success in the clinic, the endocytic mechanisms of ASO uptake by cells are still poorly understood thus limiting ASO efficacy. Therefore, improving our understanding of how ASOs are taken up and distributed in cells and tissues would help accelerate drug discovery in this field. A second emerging therapeutic strategy is the induction of Targeted Protein Degradation (TPD) of cellular targets by hijacking the intracellular proteolysis machinery. The aim of this study is to develop a method to track the delivery and distribution of ASO and/or TPD therapeutics in cells and tissues with high sensitivity and specificity at subcellular resolution based on the newest innovations in Stimulated Raman Scattering (SRS) microscopy.

反义寡核苷酸（ASO）是一种新的治疗方式，已迅速获得吸引力，目前在临床试验中大约有120种ASO，市场上有6种批准的药物。 ASOS是短的，合成的，化学修饰的寡核苷酸，与靶RNA的互补序列结合，诱导其降解或剪接过程的改变。尽管在诊所中取得了惊人的成功，但细胞对ASO摄取的内吞机制仍然很少了解，从而限制了ASO功效。因此，提高我们对如何在细胞和组织中分布ASO的理解将有助于加速该领域的药物发现。第二种新兴的治疗策略是通过劫持细胞内蛋白水解机制来诱导细胞靶标的靶向蛋白质降解（TPD）。这项研究的目的是开发一种方法，以基于刺激的拉曼散射（SRS）显微镜的最新创新，在细胞分辨率下具有高灵敏度和特异性在细胞和组织中具有高灵敏度和特异性的ASO和/或TPD疗法的分布。