DNA binding chelates for nonviral gene delivery imaging

Gene Therapy
A BogdanovR Weissleder

Abstract

Noninvasive in vivo monitoring of gene delivery would provide a critically important information regarding the spatial distribution, local concentration, kinetics of removal and/or biodegradation of the expression vector. We developed a novel approach to noninvasive gene delivery imaging using heterobifunctional peptide-based chelates (PBC) bearing double-stranded DNA-binding groups and a technetium-binding amino acid motif. One of such chelates: Gly-Cys(Acm)-Gly-Cys(Acm)-Gly-Lys(4)-Lys-(N-epsilon-[4-(psoralen-8-yloxy)]butyrate)-NH(2) has been characterized and labeled with reduced (99m)Tc pertechnetate (oxotechnetate). The psoralen moiety (a DNA binding group of PBC) allowed linking to double-stranded DNA upon short-term irradiation with the near UV range light (>320 nm). Approximately 30-40% of added (99m)Tc-labeled PBC was nonextractable and co-eluted with a model pCMV-GFP vector during the gel-permeation chromatography. Nuclear imaging of "naked" DNA and DNA complexes with lipid-based transfection reagents ("lipoplexes") has been performed after systemic or local administration of (99m)Tc-PBC-labeled DNA in mice. Imaging results were corroborated with the biodistribution using (99m)Tc-PBC and (32)P-labeled DNA and lipoplexe...Continue Reading

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Citations

Oct 29, 2002·Bioelectrochemistry·R I ZhdanovV V Vlassov
Apr 5, 2007·Nature Protocols·Yi WangDonald J Hnatowich
Apr 28, 2009·International Journal of Pharmaceutics·Clara L Santos-CuevasDavid Ordaz-Rosado
Oct 29, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eun-Mi KimIn-Joon Oh
Jul 13, 2004·Nuclear Medicine and Biology·Eun-Mi KimChang-Guhn Kim
Mar 11, 2005·Advanced Drug Delivery Reviews·Makiya NishikawaMitsuru Hashida
Apr 2, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Edmund J NiedzinskiMichael J Bennett
Apr 12, 2003·Neuroimaging Clinics of North America·Dawid Schellingerhout, Alexei A Bogdanov
Jul 31, 2007·Critical Reviews in Toxicology·Maria Luisa Scapellato, Marcello Lotti

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