title: Targeting Long Noncoding RNA with Antisense Oligonucleotide Technology as Cancer Therapeutics.
abstract: Recent annotation of the human transcriptome revealed that only 2 % of the genome encodes proteins while the majority of human genome is transcribed into noncoding RNAs. Although we are just beginning to understand the diverse roles long noncoding RNAs (lncRNAs) play in molecular and cellular processes, they have potentially important roles in human development and pathophysiology. However, targeting of RNA by traditional structure-based design of small molecule inhibitors has been difficult, due to a lack of understanding of the dynamic tertiary structures most RNA molecules adopt. Antisense oligonucleotides (ASOs) are capable of targeting specific genes or transcripts directly through Watson-Crick base pairing and thus can be designed based on sequence information alone. These agents have made possible specific targeting of "non-druggable targets" including RNA molecules. Here we describe how ASOs can be applied in preclinical studies to reduce levels of lncRNAs of interest.
authors.affiliation: Antisense Drug Discovery, Oncology, Isis Pharmaceuticals, Inc, 2855 Gazelle Court, Carlsbad, CA, 92010, USA. TZhou@isisph.com.
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Antisense Drug Discovery, Oncology, Isis Pharmaceuticals, Inc, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Antisense Drug Discovery, Oncology, Isis Pharmaceuticals, Inc, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
authors.forename: A Robert
authors.initials: AR
authors.lastname: MacLeod
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D018274:Electroporation / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use*; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C557041:MALAT1 long non-coding RNA, human; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding
keywords: Antisense oligonucleotide; Control ASO; Free uptake; Non-druggable targets; Off-target; RNA therapeutics; RNase H; Target reduction; Transfection; qRT-PCR