Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Fire, Andrew; Xu, SiQun; Montgomery, Mary K.; Kostas, Steven A.; Driver, Samuel E.; Mello, Craig C.

doi:10.1038/35888

Cited by 15,429RNA Interference and Gene DeliveryRNA Research and SplicingRNA regulation and disease

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

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Fire, Andrew, Xu, SiQun, Montgomery, Mary K., Kostas, Steven A., Driver, Samuel E., Mello, Craig C.·1998·Nature

DOI 10.1038/35888

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Abstract

Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene. Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts. RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression. Here we investigate the requirements for structure and delivery of the interfering RNA. To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually. After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference. The effects of this interference were evident in both the injected animals and their progeny. Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.

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Our approach using 500-1000 bp dsRNA builds on established protocols from model animal systems such as C. elegans and Drosophila S2 cells.
“Our approach, using 500–1000 bp dsRNA, builds on established protocols from model animal systems such as Caenorhabditis elegans and Drosophila S2 cells (Clemens et al., 2000; Fire et al., 1998).”
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RNA interference triggers degradation of particular RNA targets by double-stranded RNAs, resulting in down-regulation of corresponding proteins.
“RNA interference (RNAi) is an endogenous cellular process that triggers the degradation of particular RNA targets by double-stranded RNAs, result in the subsequent down-regulation of corresponding proteins.565–567”
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Authors: Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C.
Affiliations: Carnegie Institution for Science (US)
Johns Hopkins University (US)
University of Massachusetts Chan Medical School (US)
Corresponding author: Fire, Andrew
ORCID: Fire, Andrew
Xu, SiQun
Mello, Craig C.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1998-02
Volume: 391
Issue: 6669
Pages: 806-811
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/35888
OpenAlex: W1647075334
Cited by: 15,429
References: 27
Citations by year: 2026: 371 · 2025: 513 · 2024: 541 · 2023: 445 · 2022: 534 · 2021: 538 · 2020: 519 · 2019: 582 · 2018: 498 · 2017: 536 · 2016: 591 · 2015: 624 · 2014: 736 · 2013: 746 · 2012: 838
FWCI: 77.45
Type: journal article
Language: en
Open access: green
www.dspace.cam.ac.uk
Licence: cc-by
www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders: National Institute of General Medical Sciences (R01GM037706)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: RNA interference, double-stranded RNA, Caenorhabditis elegans, gene silencing, RNA delivery, single-stranded RNA, mRNA hybridization, interference mechanism, transgenerational inheritance
MeSH terms: Animals, Calmodulin-Binding Proteins, Gene Expression Regulation, Muscle Proteins, Phenotype, RNA, Double-Stranded, Helminth Proteins, RNA, Antisense, Caenorhabditis elegans, Genes, Helminth, Caenorhabditis elegans Proteins

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Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

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