Potency of siLAM and siLAM-peptide conjugates after PS-ON-stimulated delivery. (A) Increased dose dependent suppression of lamin A/C in ECV-304 cells after PS-stimulated delivery of siLAM-gTOX versus unconjugated siLAM. ECV-304 cells were incubated with the indicated concentrations of siLAM or siLAM-gTOX in the presence of 1 μM PS-ON 72mer for 24 h. After another 16 h in culture, cells were collected, their total RNA was extracted and reverse transcribed, and lamin A/C mRNA levels were determined by quantitative PCR. (B) Potency of siLAM-peptide conjugates to suppress lamin A/C mRNA is restricted to the conjugation of the TOX–peptide but independent of the siRNA strand carrying it. (g) Guide strand; (p) passenger strand; (mut) G → C transversion at positions 10 and 11 of the guide strand; (TOX) TQIENLKEKG; (PTS1) peroxisomal targeting signal 1, SKL.
