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
Abstract: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.