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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hao, Liangliang Choi, Chung Hang J. Narayan, Suguna P. Auyeung, Evelyn Mirkin, Chad A. |
| Description | Author Affiliation: Choi CH ( International Institute for Nanotechnology, Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.); |
| Abstract | Intracellular delivery of nucleic acids as gene regulation agents typically requires the use of cationic carriers or viral vectors, yet issues related to cellular toxicity or immune responses hamper their attractiveness as therapeutic candidates. The discovery that spherical nucleic acids (SNAs), polyanionic structures comprised of densely packed, highly oriented oligonucleotides covalently attached to the surface of nanoparticles, can effectively enter more than 50 different cell types presents a potential strategy for overcoming the limitations of conventional transfection agents. Unfortunately, little is known about the mechanism of endocytosis of SNAs, including the pathway of entry and specific proteins involved. Here, we demonstrate that the rapid cellular uptake kinetics and intracellular transport of SNAs stem from the arrangement of oligonucleotides into a 3D architecture, which supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. These results reinforce the notion that SNAs can serve as therapeutic payloads and targeting structures to engage biological pathways not readily accessible with linear oligonucleotides. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endocytosis Nanoparticles Chemistry Nucleic Acids Pharmacokinetics Animals Biological Transport Cell Line DNA, Single-Stranded Gene Transfer Techniques Genetic Vectors Membrane Microdomains Metabolism Mice Oligonucleotides RNA Interference Time Factors Transfection Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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