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Novel cationic transport agents for oligonucleotide delivery into primary leukemic cells
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SYSNO ASEP 0108989 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title Novel cationic transport agents for oligonucleotide delivery into primary leukemic cells Title Nové kationtové transportní látky pro přenos oligonukleotidů do primárních leukemických buněk Author(s) Králová, Jarmila (UMG-J) RID
Dvořák, Michal (UMG-J) RID
Král, V. (CZ)Source Title Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623
Roč. 46, č. 11 (2003), s. 2049-2056Number of pages 8 s. Language eng - English Country US - United States Keywords oligonucleotide delivery ; primary leukemic cells ; antisense effect Subject RIV EB - Genetics ; Molecular Biology R&D Projects GV301/98/K042 GA ČR - Czech Science Foundation (CSF) GA301/01/0976 GA ČR - Czech Science Foundation (CSF) GA203/02/0420 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z5052915 - UMG-J Annotation The main aim of this work was to elaborate the delivery system for oligonucleotide (ODN into primary leukemic cells. Novel cationic compounds forming complexes with ODN were prepared, and their transporting ability tested. Two cationic porphyrin derivatives (2 and 3) were found to be at least 1 order of magnitude more efficient in this respect than commercially available agents. The ODN transporting capacity of novel compounds was dependent on the magnitude and the nature of their positive charges as well as on the porphyrin/ODN molar ratio. Porphyrin-ODN complexes were internalized into cells, and their dissociation was demonstrated by accumulation of fluorescein isothiocyanate-ODN fluorescence in the nucleus. Importantly, porphyrin 3 significantly protected complexed ODN against degradation and efficiently mediated the specific antisense effect on targeted v-Myb expression, resulting in reproducible growth inhibition of treated cells. Low toxicity, serum compatibility, and water solubility of porphyrin 3 make this compound a promising novel tool for modulation of gene expression in primary leukemic cells Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2005
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