Figure 5.

Reduced Toxicity of GalNac AON Does Not Correlate with Reduced Efficacy

(A) Gene expression analysis showing PCSK9 target gene knockdown by AON-B and AON-C in their GalNAc and naked forms after 2 and 6 days of exposure in PTECs. ECs₅₀ are shown and indicate reduced potency of GalNAc AON-B and GalNAc AON-C compared to the naked counterparts. (B and C) Concentration-dependent effects of GalNAc and Naked AON-A, AON-B, and AON-C on EGF uptake (B) and intracellular ATP (C) in PTECs treated with a concentration of AON up to 500 μM for 16 days. The EGF profile at days 6 and 13 and ATP profile at day 16 showed a reduction of cytotoxic effect by GalNAc conjugation, despite the elevated concentration and extended exposure time. Data represent means and SD (n = 3).