Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus

Anthony J. Sprangers; Liangliang Hao; Resham J. Banga; Chad A. Mirkin

doi:10.1002/smll.201602753

Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus

Anthony J. Sprangers, Liangliang Hao, Resham J. Banga, Chad A. Mirkin^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

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)
Article number	1602753
Journal	Small
Volume	13
Issue number	10
DOIs	https://doi.org/10.1002/smll.201602753
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)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus",

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.",

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AU - Mirkin, Chad A.

PY - 2017/3/14

Y1 - 2017/3/14

N2 - 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.

AB - 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.

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Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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