Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles.
We present an untemplated, single-component antisense oligonucleotide delivery system capable of regulating mRNA abundance in live human cells. While most approaches to nucleic acid delivery rely on secondary carriers and complex multicomponent charge-neutralizing formulations, we demonstrate efficient delivery using a simple locked nucleic acid (LNA)-polymer conjugate that assembles into spherical micellar nanoparticles displaying a dense shell of nucleic acid at the surface. Cellular uptake of soft LNA nanoparticles occurs rapidly within minutes as evidenced by flow cytometry and fluorescence microscopy. Importantly, these LNA nanoparticles knockdown survivin mRNA, an established target for cancer therapy, in a sequence-specific fashion as analyzed by RT-PCR.
Department of Chemistry & Biochemistry, ‡Stem Cell Program and Institute for Genomic Medicine, §Department of Cellular and Molecular Medicine, ∥Department of Psychiatry, ⊥Materials Science and Engineering, University of California , San Diego, La Jolla, California 92093, United States.
Anthony M
AM
Rush
David A
DA
Nelles
Angela P
AP
Blum
Sarah A
SA
Barnhill
Erick T
ET
Tatro
Gene W
GW
Yeo
Nathan C
NC
Gianneschi
D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D009841:Oligonucleotides; D011108:Polymers; D012333:RNA, Messenger; C477371:locked nucleic acid