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. Author manuscript; available in PMC: 2019 Mar 1.
Published in final edited form as: Trends Mol Med. 2018 Feb 12;24(3):257–277. doi: 10.1016/j.molmed.2018.01.001

Key Figure, Figure 2.

Key Figure, Figure 2

Therapeutic targeting of human lncRNAs

The schematic summarizes different approaches to target lncRNAs in the nucleus and cytoplasm.

a) Transcriptional inhibition can be attained through classical CRISPR/Cas9 to delete regions of interest in lncRNA loci. Alternatively, dead-Cas9 fused to a repressor complex can inhibit transcription of lncRNA genes.

b) Transcriptional upregulation of tumor suppressors can be attained through knockdown of the corresponding Natural Antisense Transcripts (NATs). NATs can be targeted post-transcriptionally using ASOs.

c) ASOs can also be used to post-transcriptionally knockdown lncRNAs that are overexpressed in cancers.

d) Post-transcriptional silencing can also be achieved by siRNAs targeting lncRNAs. SiRNAs stimulate Dicer activity in the cytoplasm and recruit RISC complex (RNA Induced Silencing Complex) to post-transcriptionaly degrade target RNAs

e) Steric inhibition of lncRNA-protein interactions can be achieved using small molecules, morpholinos, or uniformly-modified ASOs that cannot stimulate an RNA degradation pathway.

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