title: The down regulation of target genes by photo activated DNA nanoscissors.
abstract: An artificial, targeted, light-activated nanoscissor (ATLANS) was developed for precision photonic cleavage of DNA at selectable target sequences. The ATLANS is comprised of nanoparticle core and a monolayer of hydrazone-modified triplex-forming oligonucleotides (TFOs), which recognize and capture the targeted DNA duplex. Upon photo-illumination (lambda = 460 nm), the attached hydrazone scissor specifically cleaves the targeted DNA at a pre-designed nucleotide pair. Electrophoretic mobility shift and co-precipitation assays revealed sequence-specific binding with the short-fragment and long-form plasmid DNA of both TFO and TFO-nanoparticle probes. Upon photo-illumination, ATLANS introduced a precise double-stranded break 12bp downstream the TFO binding sequence and down-regulated the target gene in HeLa cell system. Gold nanoparticles multiplexed the cutting efficiency and potential for simultaneous manipulation of multiple targets, as well as protected DNA from non-specific photo-damage. This photon-mediated DNA manipulation technology will facilitate high spatial and temporal precision in simultaneous silencing at the genome level, and advanced simultaneous manipulation of multiple targeted genes.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Tsai
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
authors.forename: Chen-Sheng
authors.initials: CS
authors.lastname: Yeh
authors.forename: Yonhua
authors.initials: Y
authors.lastname: Tzeng
authors.forename: Khant
authors.initials: K
authors.lastname: Htet
authors.forename: Kao-Shu
authors.initials: KS
authors.lastname: Chuang
authors.forename: Jih Ru
authors.initials: JR
authors.lastname: Hwu
authors.forename: Wu-Chou
authors.initials: WC
authors.lastname: Su
mesh_terms: D004247:DNA / Q000235:genetics* / Q000378:metabolism*; D053837:DNA Cleavage; D015536:Down-Regulation; D005796:Genes; D006046:Gold / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D055668:Photochemical Processes
chemical_list: D006835:Hydrazones; D006046:Gold; D004247:DNA