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Expression of ASGR1 is sufficient to mediate increased uptake and activity GalNAC-ASO conjugates in HEK 293 cells. (A) Uptake of parent and GalNAC-conjugated phosphodiester ASOs in HEK 293 cells expressing ASGR1 and/or ASGR2. (B) Uptake and activity of parent and GalNAc-conjugated phosphorothioate ASOs in ASGR1-expressing clone 1A4. GalNAc conjugation produces and 18-fold shift in IC50 that is eliminated by competing free GalNAc.
