The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
In vivo activity of nuclease-resistant siRNAs
Open accessAbstract
Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin to assess the potential utility of 2′-modified siRNAs in mammals. We demonstrate that siRNA modified with 2′-flouro (2′-F) pyrimidines are functional in cell culture and have a greatly increased stability and a prolonged half-life in human plasma as compared to 2′-OH containing siRNAs. Moreover, we show that the 2′-F containing siRNAs are functional in mice and can inhibit the expression of a target gene in vivo. However, even though the modified siRNAs have greatly increased resistance to nuclease degradation in plasma, this increase in stability did not translate into enhanced or prolonged inhibitory activity of target gene reduction in mice following tail vein injection. Thus, this study shows that 2′-F modified siRNAs are functional in vivo, but that they are not necessarily more potent than unmodified siRNAs in animals.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456
Role for a bidentate ribonuclease in the initiation step of RNA interference
Bernstein, E., Caudy, A. A., Hammond, S. M., & Hannon, G. J. (2001) · Nature · doi:10.1038/35053110 · Cited by 4,892
Hannon, G. J. (2002) · Nature · doi:10.1038/418244a · Cited by 3,538
A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants
Hamilton, A. J., & Baulcombe, D. C. (1999) · Science · doi:10.1126/science.286.5441.950 · Cited by 3,041
An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells
Hammond, S. M., Bernstein, E., Beach, D., & Hannon, G. J. (2000) · Nature · doi:10.1038/35005107 · Cited by 3,003
Zamore, P. D., Tuschl, T., Sharp, P. A., & Bartel, D. P. (2000) · Cell · doi:10.1016/s0092-8674(00)80620-0 · Cited by 2,676
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,727
Gene silencing in mammals by small interfering RNAs
McManus, M. T., & Sharp, P. A. (2002) · Nature Reviews Genetics · doi:10.1038/nrg908 · Cited by 1,399
Killing the messenger: short RNAs that silence gene expression
Dykxhoorn, D. M., Novina, C. D., & Sharp, P. A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1129 · Cited by 1,182
Cited by
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800
The chemical evolution of oligonucleotide therapies of clinical utility
Khvorova, A., & Watts, J. K. (2017) · Nature Biotechnology · doi:10.1038/nbt.3765 · Cited by 1,216
siRNA versus miRNA as therapeutics for gene silencing
Lam, J. K. W., Chow, M. Y. T., Zhang, Y., & Leung, S. W. S. (2015) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.23 · Cited by 1,081
In vivo imaging of siRNA delivery and silencing in tumors
Medarova, Z., Pham, W., Farrar, C., Petkova, V., & Moore, A. (2007) · Nature Medicine · doi:10.1038/nm1486 · Cited by 697
Metadata
- Authors
- LAYZER, J. M., MCCAFFREY, A. P., TANNER, A. K., HUANG, Z., KAY, M. A., & SULLENGER, B. A.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-04-20
- Volume
- 10
- Issue
- 5
- Pages
- 766-771
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- OpenAlex
- W2111066814
- Cited by
- 580
- References
- 27
- FWCI
- 11.59
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: In vivo activity of nuclease-resistant siRNAs. https://app.cochat.ai/papers/10.1261/rna.5239604
- The paper
- LAYZER, J. M., MCCAFFREY, A. P., TANNER, A. K., HUANG, Z., KAY, M. A., & SULLENGER, B. A. (2004). In vivo activity of nuclease-resistant siRNAs. RNA. https://doi.org/10.1261/rna.5239604
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
