Journal ArticleDOI
Cellular uptake and trafficking of antisense oligonucleotides
TLDR
Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency and the main proteins involved in these processes have been identified and intracellular sites in which PS ASOs are active, or inactive, cataloged.Abstract:
Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2' modifications can be used either as drugs (e.g., to treat homozygous familial hypercholesterolemia and spinal muscular atrophy) or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA (including mRNA and non-coding RNA) targeted by endogenous RNase H1. Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency. Cellular uptake and intracellular distribution of PS ASOs are mediated by protein interactions. The main proteins involved in these processes have been identified, and intracellular sites in which PS ASOs are active, or inactive, cataloged.read more
Citations
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RNA-Targeted Therapeutics.
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References
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Journal ArticleDOI
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Journal Article
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Nathalie Dias,Cy A. Stein +1 more
TL;DR: This chapter discusses the use of short fragments of nucleic acid, commonly called oligonucleotides, either as therapeutic agents or as tools to study gene function.
Journal Article
Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides.
TL;DR: It is demonstrated that cationic lipids increase antisense activity by increasing the amount of oligonucleotide associated with cells and altering intracellular distribution of the oligon nucleotide.