7 March 2022Differential uptake of antisense oligonucleotides in mouse hepatocytes and macrophages revealed by simultaneous 2P-fluorescence and coherent Raman imaging
Prabuddha Mukherjee,1 Edita Aksamitiene,1 Aneesh Alex,2 Jindou Shi,1 Kajari Berahttps://orcid.org/0000-0003-4094-1684,1 Chi Zhang,1 Darold R. Spillman Jr.https://orcid.org/0000-0001-9946-2659,1 Marina Marjanovic,1 Michael Fazio,3 Punit Seth,3 Kendall S. Frazier,2 Steve R. Hood,2 Stephen A. Boppart1
1Univ. of Illinois (United States) 2GlaxoSmithKline (United States) 3Ionis Pharmaceuticals, Inc. (United States)
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The primary goal of this study was to track PS-ASO and GalNAc-PS-ASO uptake in two cell cultures as the first step to understand the observations from the clinical studies. The multimodal imaging setup of CARS and 2PF modalities in conjunction with the image analysis pipeline made it uniquely possible to address these challenges. We report here the time-dependent uptake, internalization, and localization differences between GalNAc-PS-ASOs and PS-ASOs in liver cells. We believe our findings will help us form the basis for further investigations with more complex cellular co-cultures and with tissue and animal models.
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Prabuddha Mukherjee, Edita Aksamitiene, Aneesh Alex, Jindou Shi, Kajari Bera, Chi Zhang, Darold R. Spillman Jr., Marina Marjanovic, Michael Fazio, Punit Seth, Kendall S. Frazier, Steve R. Hood, Stephen A. Boppart, "Differential uptake of antisense oligonucleotides in mouse hepatocytes and macrophages revealed by simultaneous 2P-fluorescence and coherent Raman imaging," Proc. SPIE PC11938, Visualizing and Quantifying Drug Distribution in Tissue VI, PC119380D (7 March 2022); https://doi.org/10.1117/12.2608740