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Nature Milestones in Antisense RNA

The discovery of antisense RNA phenomena has profoundly altered our understanding of gene regulation and revolutionized the way biological research is conducted. The potency, specificity and ease of synthesis of antisense RNAs have made them ubiquitous and therapeutically-attractive agents in biomedical research.

This Milestone charts the history of antisense RNA breakthroughs on an interactive Timeline and provides key articles and relevant reviews from Nature Research journals. We hope you will enjoy the read!

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Milestones

Collection

Spinal muscular atrophy (SMA) is a motor neurone disease caused by a mutation in a gene called SMN1 that is necessary for the survival of motor neurons. Humans have a duplicate gene, SMN2, but that is barely expressed. One promising form of therapy involves increasing SMN2 expression. It has been assumed that it would be necessary to increase the expression of SMN2 in spinal cord motor neurons to achieve a therapeutic effect. Not so. In a mouse model of SMA, subcutaneous, peripheral administration of an antisense oligonucleotide that corrects a splicing defect in SMN2 is shown to provide a much more powerful therapy than direct delivery to the brain. Surprisingly, peripheral rescue is found to be essential for long-term rescue of SMA, and biomarkers suggest that the liver has an important role of the liver in SMA pathogenesis.

Letter | | Nature

MicroRNAs (miRNAs) are key regulators of biological processes. Recent discoveries have expanded our understanding of the control of miRNA function in animals, through alternative processing, miRNA-sequence editing, post-translational modifications of Argonaute proteins, subcellular localization and regulation of miRNA–target interactions.

Review Article | | Nature Reviews Molecular Cell Biology

Further Reading

In RNA interference, small RNAs (siRNAs or miRNAs) act to regulate gene expression. They serve as specificity factors that direct the RISC (RNA-induced silencing) complex to the complementary mRNA targets. A major component of RISC is a protein of the Argonaute family. Two groups have now identified a new class of small RNAs that interact with one Argonaute subfamily, the Piwi class. These testis-specific small RNAs, called 'piRNAs', are slightly longer than the previously described small RNAs. The function of the piRNAs is not yet known, but they might be involved in sperm production.

Letter | | Nature

In RNA interference, small RNAs (siRNAs or miRNAs) act to regulate gene expression. They serve as specificity factors that direct the RISC (RNA-induced silencing) complex to the complementary mRNA targets. A major component of RISC is a protein of the Argonaute family. Two groups have now identified a new class of small RNAs that interact with one Argonaute subfamily, the Piwi class. These testis-specific small RNAs, called 'piRNAs', are slightly longer than the previously described small RNAs. The function of the piRNAs is not yet known, but they might be involved in sperm production.

Letter | | Nature

PIWI-interacting RNAs (piRNAs) have numerous crucial biological roles, particularly transposon silencing in the germ line. In this Review, the authors describe our latest understanding of piRNA biogenesis and functions across diverse species, highlighting how, despite the universal importance of transposon control, different species have evolved intriguingly distinct mechanistic routes to achieve this.

Review Article | | Nature Reviews Genetics

CRISPR–Cas systems have revolutionized genome editing, and the CRISPR–Cas toolkit has been expanding to include single-base editing enzymes, targeting RNA and fusing inactive Cas proteins to effectors that regulate various nuclear processes. Consequently, CRISPR–Cas systems are being tested for gene and cell therapies.

Review Article | | Nature Reviews Molecular Cell Biology

Two decades after antisense oligonucleotides (ASOs) were initially identified as agents capable of modulating RNA processing and protein expression, the first antisense oligonucleotide (ASO) therapies have now been approved for the treatment of neurological disease. Here, Rinaldi and Wood discuss our current understanding of ASO pharmacology, and the future prospects for ASO-mediated treatment of neurological disease

Review Article | | Nature Reviews Neurology

The recent approval of the first RNA interference (RNAi)-based therapy has generated considerable excitement in the field. Here, Rossi and colleagues discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, assess the current clinical pipeline and highlight future opportunities and challenges for RNAi-based therapeutics.

Review Article | | Nature Reviews Drug Discovery