Extended Data Fig. 1: Characterizing different routes of siRNA<(EG18L)2 delivery in PTOA mouse model.
a-c, Subcutaneous delivery of Cy5-siRNA<(EG18L)2 (2 mg/kg) was administered in a PTOA mouse model. Timeline for mechanical knee loading and treatment is shown (a). Intravital (b) and ex vivo (c) Cy5 fluorescence imaging was used to measure Cy5-siRNA<(EG18L)2 biodistribution to paired healthy and PTOA knees, along with organs, 24 hrs after subcutaneous treatment. N = 3. d, Quantification of subcutaneous vs. intravenous (i.v.) delivery route organ biodistribution 24 h after injection. Analyzed using multiple unpaired t-tests with no correction for multiple comparisons. e-g, Intra-articular delivery of Cy5-siRNA<(EG18L)2 (0.25 mg/kg) was characterized in a PTOA mouse model. Timeline for mechanical knee loading and treatment is shown (e). Ex vivo Cy5 fluorescence imaging was used to measure Cy5-siRNA<(EG18L)2 biodistribution to paired healthy and loaded knees, along with organs, 48 hrs after delivery (f). N = 3. Analyzed using multiple unpaired t-tests with no correction for multiple comparisons. (g) Cryohistology of the loaded knee joints 48 h after intra-articular injection with a focus on cartilage and synovial tissues. N = 3. Dashed lines outline articular cartilage. For all panels: Error bars indicate standard deviation of biological replicates. Radiant efficiency units are [photons/s] / [µW/cm²]. Knees labeled healthy indicate a non-loaded contralateral limb (right).
