In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides
| Autor: | Marja E. Jakobs, Marit B. de Wissel, Otto Olsen, Anneloor L.M.A. ten Asbroek, Margit Wissenbach, Håkan Olsson, Henrik Oerum, Frank Baas, Kees Fluiter |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, Human Genetics, Genome Analysis, Faculteit der Geneeskunde |
| Rok vydání: | 2003 |
| Předmět: |
Biodistribution
Mice Nude Biology chemistry.chemical_compound Mice In vivo Genetics Tumor Cells Cultured Animals Tissue Distribution Locked nucleic acid POLR2A Oligonucleotide hemic and immune systems Neoplasms Experimental Articles respiratory system Oligonucleotides Antisense Molecular biology Xenograft Model Antitumor Assays In vitro chemistry Nucleic acid sense organs RNA Polymerase II DNA Cell Division |
| Zdroj: | Nucleic acids research, 31(3), 953-962. Oxford University Press Nucleic Acids Research, 31(3), 953-962. Oxford University Press |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely synthesized as LNA containing diester backbones. These full LNA oligonucleotides strongly reduce POLR2A protein levels. Full LNA PO ODNs appeared to be very stable compounds when injected into the circulation of mice. Full LNA PO ODNs were continuously administered for 14 days to tumor-bearing nude mice. Tumor growth was inhibited sequence specifically at dosages from 1 mg/kg/day. LNA PO ODNs appeared to be non-toxic at dosages |
| Databáze: | OpenAIRE |
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