title: Cellular uptake and trafficking of antisense oligonucleotides.
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.
authors.affiliation: Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
authors.forename: Stanley T
authors.initials: ST
authors.lastname: Crooke
authors.affiliation: Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Vickers
authors.affiliation: Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
authors.forename: Xue-Hai
authors.identifier: http://orcid.org/0000-0001-9333-8622
authors.initials: XH
authors.lastname: Liang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense