NSTI Nanotech 2009

Targeted photonic manipulation of DNA by nanoscissors

D.-B. Shieh, T.-L. Tsai, K.-S. Chuang, C.-S. Yeh, Y. Tzeng, K.T. Li, W.-C. Su, J.-R. Hwu
National Cheng kung University, TW

Keywords: DNA, targeting therapy, nanoscissor, triplex forming oligonucleotide


We recently reported improved photonic cleavage of DNA by the “mace effect” of nanoparticles conjugated hydrazone compounds. In this report, we successfully developed precision molecular surgery of DNA through sequence-specific recognition of the target DNA duplex by triplex forming oligonucleotide (TFO). This artificial, targeted, light-activated nano-scissors (ATLANS) shows photo induced double-strand DNA cleavage at 12 bp upstream of the 3’-end of the TFO sequence. The nanoscissor composed of a nano-particle core that enables multiplexing of the cutting efficiency, potential simultaneous manipulation of multiple targets, and reduction of non-specific photo-damage. There is a monolayer of hydrazone-modified outwardly extended TFO that recognized, captured, and cleaved the targeted DNA duplex when it was illuminated by a wavelength (460 nm) tailored for improved tissue penetration when using two-photon technology (920 nm) at NIR biological optical window spectra range. By combining precision laser activation at a specific region of interest, simultaneous genome-level silencing of multiple targeted genes in desired cells should be possible in gene therapies.
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