The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation
Open accessAbstract
Gene silencing by double-stranded RNA, denoted RNA interference, represents a new paradigm for rational drug design. However, the transformative therapeutic potential of short interfering RNA (siRNA) has been stymied by a key obstacle—safe delivery to specified target cells in vivo. Macrophages are particularly attractive targets for RNA interference therapy because they promote pathogenic inflammatory responses in diseases such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and diabetes. Here we report the engineering of β1,3-d-glucan-encapsulated siRNA particles (GeRPs) as efficient oral delivery vehicles that potently silence genes in mouse macrophages in vitro and in vivo. Oral gavage of mice with GeRPs containing as little as 20 μg kg-1 siRNA directed against tumour necrosis factor α (Tnf-α) depleted its messenger RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and lowered serum Tnf-α levels. Screening with GeRPs for inflammation genes revealed that the mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) is a previously unknown mediator of cytokine expression. Importantly, silencing Map4k4 in macrophages in vivo protected mice from lipopolysaccharide-induced lethality by inhibiting Tnf-α and interleukin-1β production. This technology defines a new strategy for oral delivery of siRNA to attenuate inflammatory responses in human disease.
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
LPS/TLR4 signal transduction pathway
Lu, Y.-C., Yeh, W.-C., & Ohashi, P. S. (2008) · Cytokine · doi:10.1016/j.cyto.2008.01.006 · Cited by 3,301
Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., Elbashir, S., Geick, A., Hadwiger, P., Harborth, J., et al. (2004) · Nature · doi:10.1038/nature03121 · Cited by 2,183
The immune response in atherosclerosis: a double-edged sword
Hansson, G. K., & Libby, P. (2006) · Nature Reviews Immunology · doi:10.1038/nri1882 · Cited by 2,182
RNAi-mediated gene silencing in non-human primates
Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357
RNA interference in adult mice
McCaffrey, A. P., Meuse, L., Pham, T.-T. T., Conklin, D. S., Hannon, G. J., & Kay, M. A. (2002) · Nature · doi:10.1038/418038a · Cited by 1,059
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors
Song, E., Zhu, P., Lee, S.-K., Chowdhury, D., Kussman, S., Dykxhoorn, D. M., Feng, Y., Palliser, D., Weiner, D. B., Shankar, P., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1101 · Cited by 1,021
Okusawa, S., Gelfand, J. A., Ikejima, T., Connolly, R. J., & Dinarello, C. A. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113431 · Cited by 983
Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes
Vazquez-Torres, A., Jones-Carson, J., Bäumler, A. J., Falkow, S., Valdivia, R., Brown, W., Le, M., Berggren, R., Parks, W. T., & Fang, F. C. (1999) · Nature · doi:10.1038/44593 · Cited by 683
Frank-Kamenetsky, M., Grefhorst, A., Anderson, N. N., Racie, T. S., Bramlage, B., Akinc, A., Butler, D., Charisse, K., Dorkin, R., Fan, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805434105 · Cited by 642
Cited by
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269
Macrophages in the Pathogenesis of Atherosclerosis
Moore, K. J., & Tabas, I. (2011) · Cell · doi:10.1016/j.cell.2011.04.005 · Cited by 2,669
Therapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839
Metabolic functions of FABPs—mechanisms and therapeutic implications
Hotamisligil, G. S., & Bernlohr, D. A. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.122 · Cited by 712
Wilson, D. S., Dalmasso, G., Wang, L., Sitaraman, S. V., Merlin, D., & Murthy, N. (2010) · Nature Materials · doi:10.1038/nmat2859 · Cited by 747
Metadata
- Authors
- Aouadi, M., Tesz, G. J., Nicoloro, S. M., Wang, M., Chouinard, M., Soto, E., Ostroff, G. R., & Czech, M. P.
- Venue
- Nature
- Published
- 2009-04
- Volume
- 458
- Issue
- 7242
- Pages
- 1180-1184
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1999732094
- Cited by
- 573
- References
- 31
- FWCI
- 17.28
- Type
- journal article
- Language
- en
- Open access
- green
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: Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. https://app.cochat.ai/papers/10.1038/nature07774
- The paper
- Aouadi, M., Tesz, G. J., Nicoloro, S. M., Wang, M., Chouinard, M., Soto, E., Ostroff, G. R., & Czech, M. P. (2009). Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature. https://doi.org/10.1038/nature07774
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.
