Figure 1.

Stereopure oligonucleotide (MALAT1-200) is more potent than a sequence- and chemistry-matched stereorandom oligonucleotide control in vitro. (A) Schematics of stereorandom (MALAT1-181) and stereopure (MALAT1-200) oligonucleotides are shown. The backbone stereochemistry differs, but the sequences and the chemical modifications are identical. MALAT1-181 is a mixture of over 65,000 stereoisomers (Supplementary Fig. S1 and Supplementary Table S1). (B) Time-dependent activity of RNase H1 in vitro on heteroduplexes formed between a complementary Malat1 RNA and the stereopure (MALAT1-200) or stereorandom (MALAT1-181) oligonucleotide. Initial velocities (V₀) were calculated from the slopes of the lines (n = 3 per time point). (C) Relative expression of MALAT1 in iCell neurons after treatment with increasing concentrations of stereorandom or stereopure oligonucleotide. Half-maximal inhibitory concentrations (IC₅₀s) were calculated from the best-fit curves (n = 2 per treatment concentration).