As RNA therapeutics expand beyond the liver into the CNS and peripheral tissues, development decisions increasingly require more than total tissue exposure.
A central question is whether siRNA reaches relevant cell populations and shows evidence of molecular target engagement in those cells within their native tissue architecture.
This webinar will examine how RNAscope-based target-RNA detection, together with sequence-specific ISH and other spatial approaches for therapeutic oligonucleotide detection, can be combined with multiplex
imaging and digital pathology.
Drawing on preclinical and translational examples, Xavier Langa will discuss strategies to assess cellular distribution, target-RNA modulation, and cell identity across CNS and peripheral organs.
The session will focus on practical study design, panel optimization, quality controls, and fit-for-purpose quantitative image-analysis workflows for RNAscope and multiplex imaging data.
Attendees will learn how to define biologically meaningful endpoints; perform tissue and cell segmentation; quantify punctate RNA and marker signals; apply robust quality control and thresholding; and generate reproducible, interpretable cell- and compartment-level results.
Key Learnings:
- Distinguish total tissue exposure, cellular accumulation, spatial evidence of target engagement, and productive intracellular delivery when interpreting siRNA images.
- Design multiplex ISH/mIF panels that enable cell- and compartment-resolved assessment of therapeutic-associated signal, target RNA, and cell identity.
- Select and validate RNAscope/ISH controls, image-acquisition settings, tissue annotations, and signal thresholds for robust, reproducible quantitative analysis.
- Develop reproducible workflows to quantify RNAscope and multiplex imaging data—from tissue annotation and cell identification to RNA-signal measurement and quality control.
- Transform image-derived measurements into biologically meaningful cell- and compartment-level quantitative endpoints using appropriate units of analysis, data aggregation, and visualization.
