The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
siRNA and Innate Immunity
Abstract
Canonical small interfering RNA (siRNA) duplexes are potent activators of the mammalian innate immune system. The induction of innate immunity by siRNA is dependent on siRNA structure and sequence, method of delivery, and cell type. Synthetic siRNA in delivery vehicles that facilitate cellular uptake can induce high levels of inflammatory cytokines and interferons after systemic administration in mammals and in primary human blood cell cultures. This activation is predominantly mediated by immune cells, normally via a Toll-like receptor (TLR) pathway. The siRNA sequence dependency of these pathways varies with the type and location of the TLR involved. Alternatively nonimmune cell activation may also occur, typically resulting from siRNA interaction with cytoplasmic RNA sensors such as RIG1. As immune activation by siRNA-based drugs represents an undesirable side effect due to the considerable toxicities associated with excessive cytokine release in humans, understanding and abrogating this activity will be a critical component in the development of safe and effective therapeutics. This review describes the intracellular mechanisms of innate immune activation by siRNA, the design of appropriate sequences and chemical modification approaches, and suitable experimental methods for studying their effects, with a view toward reducing siRNA-mediated off-target effects.
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Dowdy, S. F. (2017) · Nature Biotechnology · doi:10.1038/nbt.3802 · Cited by 1,139
Jackson, A. L., & Linsley, P. S. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3010 · Cited by 1,083
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
Crooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841
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Metadata
- Authors
- Robbins, M., Judge, A., & MacLachlan, I.
- Venue
- Oligonucleotides
- Publisher
- SAGE Publications
- Published
- 2009-06
- Volume
- 19
- Issue
- 2
- Pages
- 89-102
- ISSN
- 1545-4576 (ISSN-L)
- 1557-8526
- OpenAlex
- W2038660811
- Cited by
- 449
- References
- 16
- FWCI
- 16.08
- 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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