Abstract
Emerging evidence indicates that long noncoding RNAs (lncRNAs) are actively involved in a number of developmental and tumorigenic processes. Here, the authors describe the first successful use of spherical nucleic acids as an effective nanoparticle platform for regulating lncRNAs in cells; specifically, for the targeted knockdown of the nuclear-retained metastasis associated lung adenocarcinoma transcript 1 (Malat1), a key oncogenic lncRNA involved in metastasis of several cancers. Utilizing the liposomal spherical nucleic acid (LSNA) constructs, the authors first explored the delivery of antisense oligonucleotides to the nucleus. A dose-dependent inhibition of Malat1 upon LSNA treatment as well as the consequent up-regulation of tumor suppressor messenger RNA associated with Malat1 knockdown are shown. These findings reveal the biologic and therapeutic potential of a LSNA-based antisense strategy in targeting disease-associated, nuclear-retained lncRNAs.
Original language | English (US) |
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Article number | 1602753 |
Journal | Small |
Volume | 13 |
Issue number | 10 |
DOIs | |
State | Published - Mar 14 2017 |
Funding
This research was supported by the National Cancer Institute of the National Institutes of Health under Award Number U54CA199091. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This material is also based upon work supported by the NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, USA and the Nanyang Technological University, Singapore. A.J.S. acknowledges the NSF Graduate Research Fellowship. L.H. was a Howard Hughes Medical Institute International Student Research Fellow and acknowledges a Ryan Fellowship from Northwestern University. Confocal imaging was performed at the Biological Imaging Facility (BIF) at Northwestern University.
Keywords
- DNA nanoparticles
- gene regulation
- liposomal SNA
- nuclear targeting
- spherical nucleic acids
ASJC Scopus subject areas
- Biotechnology
- General Chemistry
- Biomaterials
- General Materials Science
- Engineering (miscellaneous)