Cuiwen He, Michael T Migawa, Kai Chen, Thomas A Weston, Michael Tanowitz, Wenxin Song, Paul Guagliardo, K Swaminathan Iyer, C Frank Bennett, Loren G Fong, Punit P Seth, Stephen G Young, and Haibo Jiang
Nucleic Acids Research, gkaa1112, https://doi.org/10.1093/nar/gkaa1112
In this study, the authors develop and apply stable isotope/elemental labeling of Nucleic Acid-Based Therapeutics (‘NATs’) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging for studies of NAT pharmacokinetics in cells and tissues. They focus on the behavior of antisense oligonucleotides (ASOs), as their uptake and distribution has been extensively characterized by multiple techniques. The study provides three major scientific advances: (1) high-resolution visualization of the distribution of ASOs delivered to cells without transfection reagents; (2) visualization of ASO distribution within tissues after only a single subcutaneous injection; and (3) new biochemical insights into ASO trafficking and distribution.