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Making sense of antisense oligonucleotides: A narrative review
Author(s) -
Goyal Neelam,
Narayanaswami Pushpa
Publication year - 2018
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.26001
Subject(s) - spinal muscular atrophy , oligonucleotide , nucleic acid , rna , amyotrophic lateral sclerosis , antisense therapy , muscular dystrophy , medicine , sense (electronics) , biology , pharmacology , genetics , computational biology , dna , gene , bioinformatics , chemistry , disease , pathology , locked nucleic acid
Synthetic nucleic acid sequences that bind to ribonucleic acid (RNA) through Watson‐Crick base pairing are known as antisense oligonucleotides (ASOs) because they are complementary to “sense strand” nucleic acids. ASOs bind to selected sequences of RNA and regulate the expression of genes by several mechanisms depending on their chemical properties and targets. They can be used to restore deficient protein expression, reduce the expression of a toxic protein, modify functional effects of proteins, or reduce toxicity of mutant proteins. Two ASOs were approved by the U.S. Food and Drug Administration in 2016: eteplirsen for Duchenne muscular dystrophy and nusinersen for spinal muscular atrophy. Clinical trials in amyotrophic lateral sclerosis and familial amyloid polyneuropathy are ongoing. We review the chemistry, pharmacology, and mechanisms of action of ASOs, preclinical data, and clinical trials in neuromuscular diseases and discuss some ethical, regulatory, and policy considerations in the clinical development and use of ASOs. Muscle Nerve 57 : 356–370, 2018