The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes
Open accessAbstract
Achieving efficient in vivo delivery of siRNA to the appropriate target cell would be a major advance in the use of RNAi in gene function studies and as a therapeutic modality. Hepatocytes, the key parenchymal cells of the liver, are a particularly attractive target cell type for siRNA delivery given their central role in several infectious and metabolic disorders. We have developed a vehicle for the delivery of siRNA to hepatocytes both in vitro and in vivo , which we have named siRNA Dynamic PolyConjugates. Key features of the Dynamic PolyConjugate technology include a membrane-active polymer, the ability to reversibly mask the activity of this polymer until it reaches the acidic environment of endosomes, and the ability to target this modified polymer and its siRNA cargo specifically to hepatocytes in vivo after simple, low-pressure i.v. injection. Using this delivery technology, we demonstrate effective knockdown of two endogenous genes in mouse liver: apolipoprotein B ( apoB ) and peroxisome proliferator-activated receptor alpha ( ppara ). Knockdown of apoB resulted in clear phenotypic changes that included a significant reduction in serum cholesterol and increased fat accumulation in the liver, consistent with the known functions of apoB . Knockdown of ppara also resulted in a phenotype consistent with its known function, although with less penetrance than observed in apoB knockdown mice. Analyses of serum liver enzyme and cytokine levels in treated mice indicated that the siRNA Dynamic PolyConjugate was nontoxic and well tolerated.
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Cites
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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
Knocking down barriers: advances in siRNA delivery
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In vivo genome editing using Staphylococcus aureus Cas9
Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., Zetsche, B., Shalem, O., Wu, X., Makarova, K. S., et al. (2015) · Nature · doi:10.1038/nature14299 · Cited by 2,687
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
Therapeutic siRNA: state of the art
Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0207-x · Cited by 1,586
Metadata
- Authors
- Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., Hagstrom, J. E., & Wolff, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-08-07
- Volume
- 104
- Issue
- 32
- Pages
- 12982-12987
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2048369172
- Cited by
- 658
- References
- 51
- FWCI
- 14.97
- Type
- journal article
- Language
- en
- Open access
- green
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- Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., Hagstrom, J. E., & Wolff, J. A. (2007). Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0703778104
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