The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Overcoming the Innate Immune Response to Small Interfering RNA
Abstract
Many types of nucleic acid, including canonical small interfering RNA (siRNA) duplexes, are potent activators of the mammalian innate immune system. Synthetic siRNA duplexes can induce high levels of inflammatory cytokines and type I interferons, in particular interferon-alpha, after systemic administration in mammals and in primary human blood cell cultures. These responses are greatly potentiated by the use of delivery vehicles that facilitate cellular uptake of the siRNA. Although the immunomodulatory effects of nucleic acids may be harnessed therapeutically, for example, in oncology and allergy applications, in many cases immune activation represents a significant undesirable side effect due to the toxicities associated with excessive cytokine release and associated inflammatory syndromes. The potential for siRNA-based drugs to be rendered immunogenic is also a cause for concern because the establishment of an antibody response may severely compromise both safety and efficacy. Clearly, there are significant implications both for the development of siRNA-based drugs and in the interpretation of gene-silencing effects elicited by siRNA. This review provides the background information required to anticipate, manage, and abrogate the immunological effects of siRNA and will assist the reader in the successful in vivo application of siRNA-based drugs.
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Cites
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C. (2004) · Science · doi:10.1126/science.1093616 · Cited by 3,444
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728
RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210
Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412
Suntharalingam, G., Perry, M. R., Ward, S., Brett, S. J., Castello-Cortes, A., Brunner, M. D., & Panoskaltsis, N. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa063842 · Cited by 2,164 · cited 1×
“These symptoms were subsequently attributed to “on-target” effects of the CD28 agonist causing excessive cytokine release, leading to a severe shocklike syndrome (Suntharalingam et al., 2006).”
Innate immune recognition of viral infection
Kawai, T., & Akira, S. (2006) · Nature Immunology · doi:10.1038/ni1303 · Cited by 1,899
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677 · cited 2×
“Treatment of humans with OVERCOMING IMMUNE RESPONSES TO siRNA TLR ligands such as LPS (TLR4) (Michie et al ., 1988; Lynn et al ., 2003) or poly(I:C) (TLR3) (Stevenson et al ., 1985) re-sults in an inflammatory response syndrome characterized by flulike symptoms, fever, chills, rigors, and hypotension.”
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
Cited by
Jackson, A. L., & Linsley, P. S. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3010 · Cited by 1,083
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656
Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity
Whitehead, K. A., Dorkin, J. R., Vegas, A. J., Chang, P. H., Veiseh, O., Matthews, J., Fenton, O. S., Zhang, Y., Olejnik, K. T., Yesilyurt, V., et al. (2014) · Nature Communications · doi:10.1038/ncomms5277 · Cited by 615
Kedmi, R., Ben-Arie, N., & Peer, D. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.05.027 · Cited by 546
Silencing disease genes in the laboratory and the clinic
Watts, J. K., & Corey, D. R. (2012) · The Journal of Pathology · doi:10.1002/path.2993 · Cited by 470
Metadata
- Authors
- Judge, A., & MacLachlan, I.
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2008-02
- Volume
- 19
- Issue
- 2
- Pages
- 111-124
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W1992517046
- Cited by
- 284
- References
- 12
- FWCI
- 13.28
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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