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

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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.