As shown in Figure 6B , the (R-Ahx-R) 4 -PMO-FAM conjugate was widely distributed within the cell with a clear accumulation in nuclei in saponin-permeabilized cells. These low molecular mass conjugates are indeed expected to diffuse freely and rapidly from the cytoplasm to the nuclei through the nuclear pores. In a different protocol, cells were loaded with Alexa-labeled Transferrin (a known marker of endosomes) and then treated with saponin. At variance with the wide distribution of the CPP-PMO-FAM conjugates, Transferrin-associated red fluorescence remained punctate in keeping with the reported minimal effects of saponin on intracellular architecture ( Figure 6C ). Along the same lines, we have verified that saponin did not lead to a significant release of (R-Ahx-R) 4 -PMO conjugate preloaded in endocytic vesicles (data not shown).