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dc.contributor.authorCui, Lina
dc.contributor.authorCohen, Jessica L.
dc.contributor.authorChu, Crystal K.
dc.contributor.authorWich, Peter R.
dc.contributor.authorKierstead, Paul H.
dc.contributor.authorFrechet, Jean
dc.date.accessioned2015-08-03T10:01:16Z
dc.date.available2015-08-03T10:01:16Z
dc.date.issued2012-09-18
dc.identifier.citationCui, L., Cohen, J. L., Chu, C. K., Wich, P. R., Kierstead, P. H., & Fréchet, J. M. J. (2012). Conjugation Chemistry through Acetals toward a Dextran-Based Delivery System for Controlled Release of siRNA. Journal of the American Chemical Society, 134(38), 15840–15848. doi:10.1021/ja305552u
dc.identifier.issn00027863
dc.identifier.pmid22958132
dc.identifier.doi10.1021/ja305552u
dc.identifier.urihttp://hdl.handle.net/10754/562333
dc.description.abstractNew conjugation chemistry for polysaccharides, exemplified by dextran, was developed to enable the attachment of therapeutic or other functional moieties to the polysaccharide through cleavable acetal linkages. The acid-lability of the acetal groups allows the release of therapeutics under acidic conditions, such as that of the endocytic compartments of cells, regenerating the original free polysaccharide in the end. The physical and chemical behavior of these acetal groups can be adjusted by modifying their stereoelectronic and steric properties, thereby providing materials with tunable degradation and release rates. We have applied this conjugation chemistry in the development of water-soluble siRNA carriers, namely acetal-linked amino-dextrans, with various amine structures attached through either slow- or fast-degrading acetal linker. The carriers with the best combination of amine moieties and structural composition of acetals showed high in vitro transfection efficiency and low cytotoxicity in the delivery of siRNA. © 2012 American Chemical Society.
dc.description.sponsorshipThis work was funded through Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract No. HHSN268201000043C), and the Frechet "various donors" gift fund for the support of research in new materials. P. R. Wich gratefully acknowledges the Alexander von Humboldt Foundation (AvH) for funding. We also thank A. Fischer in the UC Berkeley Cell Culture Facility for her help with cell culture preparation.
dc.publisherAmerican Chemical Society (ACS)
dc.titleConjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA
dc.typeArticle
dc.contributor.departmentChemical Science Program
dc.contributor.departmentOffice of the VP
dc.contributor.departmentPhysical Science and Engineering (PSE) Division
dc.identifier.journalJournal of the American Chemical Society
dc.contributor.institutionCollege of Chemistry, University of California, Berkeley, CA 94720-1460, United States
dc.contributor.institutionMolecular Imaging Program, School of Medicine, Stanford University, Stanford, CA 94305, United States
kaust.personFrechet, Jean
dc.date.published-online2012-09-18
dc.date.published-print2012-09-26


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