The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
The Effect of Chemical Modification and Nanoparticle Formulation on Stability and Biodistribution of siRNA in Mice
Open accessAbstract
Instability and inadequate biodistribution of double-stranded RNA are major drawbacks to the clinical use of RNA interference. This work compares chemical modification and nanoparticle formulation as strategies to improve the systemic delivery of small interfering RNA (siRNA). Variable levels of chemical modified siRNA, either naked or within nanoparticle, were intravenously injected into mice to study temporal stability and biodistribution detected by direct radioactive labeling or by northern blotting. Naked siRNA showed rapid renal clearance, with circulatory half-life of <5 minutes that could be extended to >30 minutes by cholesterol conjugation. The integrity of the chemically stabilized siRNA was maintained in blood for at least 30 minutes, whereas, unmodified siRNA duplex was degraded within 1 minute. Intact chemically modified siRNA could also be detected in all analyzed organs at 30 minutes but disappeared at 24 hours, except for heavy locked nucleic acid (LNA)-modified and cholesterol-conjugated siRNA in the lungs. Chitosan, liposomal, or JetPEI formulation greatly improved the stability and biodistribution of siRNA. Interestingly, high siRNA accumulation of the chitosan/siRNA formulation within the kidney was observed 24 hours postadministration. This comparative study highlights improvements to siRNA stability and pharmacokinetics, key determinants for development of clinically relevant RNAi therapeutics.
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Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
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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
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Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery
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RNA Interference in Vitro and in Vivo Using a Novel Chitosan/siRNA Nanoparticle System
Howard, K. A., Rahbek, U. L., Liu, X., Damgaard, C. K., Glud, S. Z., Andersen, M. Ø., Hovgaard, M. B., Schmitz, A., Nyengaard, J. R., Besenbacher, F., et al. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.04.010 · Cited by 585
Self-citationLocked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
Elm n, J. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki193 · Cited by 559
Formation and Intracellular Trafficking of Lipoplexes and Polyplexes
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The growth of siRNA-based therapeutics: updated clinical studies
Zhang, M. M., Bahal, R., Rasmussen, T. P., Manautou, J. E., & Zhong, X.-B. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114432 · Cited by 497
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Action and Reaction: The Biological Response to siRNA and Its Delivery Vehicles
Kanasty, R. L., Whitehead, K. A., Vegas, A. J., & Anderson, D. G. (2012) · Molecular Therapy · doi:10.1038/mt.2011.294 · Cited by 279
Small interfering RNA: Discovery, pharmacology and clinical development—An introductory review
Ranasinghe, P., Addison, M. L., Dear, J. W., & Webb, D. J. (2023) · British Journal of Pharmacology · doi:10.1111/bph.15972 · Cited by 138
Metadata
- Authors
- Gao, S., Dagnaes-Hansen, F., Nielsen, E. J. B., Wengel, J., Besenbacher, F., Howard, K. A., & Kjems, J.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 17
- Issue
- 7
- Pages
- 1225-1233
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2159887227
- Cited by
- 286
- References
- 42
- FWCI
- 7.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
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