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Liposomal Spherical Nucleic Acids for Regulating Long Noncoding RNAs in the Nucleus
Author(s) -
Sprangers Anthony J.,
Hao Liangliang,
Banga Resham J.,
Mirkin Chad A.
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201602753
Subject(s) - gene knockdown , nucleic acid , rna , biology , microrna , malat1 , oligonucleotide , long non coding rna , metastasis , cancer research , microbiology and biotechnology , cancer , biochemistry , dna , apoptosis , gene , genetics
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.