Emerging evidence indicates that long noncoding RNAs (lncRNAs) are actively involved in a number of developmental and tumorigenic processes. Here, Northwestern University researchers 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 researchers 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.
The Cy5 MFI was quantified at the center of the nucleus in A549 cells. Z-stacks were generated with optical sections of 0.3 µm throughout the cell. When measuring the MFI intensity with the nucleus (yellow circle), we used the peaks in the DAPI MFI versus Z-Displacement graph to identify the top and bottom of the nucleus (green line). The center of the nucleus was defined as the midpoint between these two edges (yellow line) where the Cy5 MFI was recorded.