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Identification and characterization of receptor-specific peptides for siRNA delivery

Author(s)
Ren, Yin; Hauert, Sabine; Lo, Justin H.; Bhatia, Sangeeta N
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Abstract
Tumor-targeted delivery of siRNA remains a major barrier in fully realizing the therapeutic potential of RNA interference. While cell-penetrating peptides (CPP) are promising siRNA carrier candidates, they are universal internalizers that lack cell-type specificity. Herein, we design and screen a library of tandem tumor-targeting and cell-penetrating peptides that condense siRNA into stable nanocomplexes for cell type-specific siRNA delivery. Through physiochemical and biological characterization, we identify a subset of the nanocomplex library of that are taken up by cells via endocytosis, trigger endosomal escape and unpacking of the carrier, and ultimately deliver siRNA to the cytosol in a receptor-specific fashion. To better understand the structure–activity relationships that govern receptor-specific siRNA delivery, we employ computational regression analysis and identify a set of key convergent structural properties, namely the valence of the targeting ligand and the charge of the peptide, that help transform ubiquitously internalizing cell-penetrating peptides into cell type-specific siRNA delivery systems.
Date issued
2012-08
URI
http://hdl.handle.net/1721.1/75316
Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Koch Institute for Integrative Cancer Research at MIT
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
Citation
Ren, Yin et al. “Identification and Characterization of Receptor-Specific Peptides for siRNA Delivery.” ACS Nano 6.10 (2012): 8620–8631. Copyright © 2012 American Chemical Society
Version: Final published version
ISSN
1936-0851
1936-086X

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