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. 2017 Apr 1;27(2):70–77. doi: 10.1089/nat.2016.0656

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© Stanley T. Crooke, 2017; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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FIG. 1. — Rates of steps in RNase H1 activating ASOs activity [11]. (A) After transfection, about 60 min is required for intracellular distribution of ASOs. In both the nucleus and cytoplasm, about 20 min are required to screen nucleic acid sequence and bind to the cognate site. Approximately 40 min are then required to recruit RNase H1 and achieve measurable RNA target reduction. (B) The transcription and splicing rates for the wild-type SOD1 construct and a mutant (187) with substantially reduced splicing. (C) An effective RNase H1 activating ASO approximately doubles the intrinsic rate of cellular RNA degradation. (D) The concentration of RNAse H1 is rate limiting. Over-expression of Escherichia coli RNase H1 again doubles the rate reduction induced by an effective RNase H1 ASO. ASO, antisense oligonucleotide.

FIG. 1. — Rates of steps in RNase H1 activating ASOs activity [11]. (A) After transfection, about 60 min is required for intracellular distribution of ASOs. In both the nucleus and cytoplasm, about 20 min are required to screen nucleic acid sequence and bind to the cognate site. Approximately 40 min are then required to recruit RNase H1 and achieve measurable RNA target reduction. (B) The transcription and splicing rates for the wild-type SOD1 construct and a mutant (187) with substantially reduced splicing. (C) An effective RNase H1 activating ASO approximately doubles the intrinsic rate of cellular RNA degradation. (D) The concentration of RNAse H1 is rate limiting. Over-expression of Escherichia coli RNase H1 again doubles the rate reduction induced by an effective RNase H1 ASO. ASO, antisense oligonucleotide.

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