Potent and nontoxic antisense oligonucleotides containing locked nucleic acids
نویسندگان
چکیده
منابع مشابه
Design of antisense oligonucleotides stabilized by locked nucleic acids.
The design of antisense oligonucleotides containing locked nucleic acids (LNA) was optimized and compared to intensively studied DNA oligonucleotides, phosphorothioates and 2'-O-methyl gapmers. In contradiction to the literature, a stretch of seven or eight DNA monomers in the center of a chimeric DNA/LNA oligonucleotide is necessary for full activation of RNase H to cleave the target RNA. For ...
متن کاملDesign and characterization of decoy oligonucleotides containing locked nucleic acids.
Transfection of cis-element double-stranded oligonucleotides, referred to as decoy ODNs, has been reported to be a powerful tool that provides a new class of antigene strategies for gene therapy. However, one of the major limitations of the decoy approach is the rapid degradation of phosphodiester oligonucleotides by intracellular nucleases. To date, several DNA analogs have been employed to ov...
متن کاملAntisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals
A series of antisense oligonucleotides (ASOs) containing either 2'-O-methoxyethylribose (MOE) or locked nucleic acid (LNA) modifications were designed to investigate whether LNA antisense oligonucleotides (ASOs) have the potential to improve upon MOE based ASO therapeutics. Some, but not all, LNA containing oligonucleotides increased potency for reducing target mRNA in mouse liver up to 5-fold ...
متن کاملLocked Nucleic Acids (LNAs)
With few exceptions, experimental success in molecular biology is dependent upon specific, discriminating, and persistent hybridization events involving synthetic oligonucleotides and their complementary target sequences. While unmodified oligodeoxynucleotides will routinely form desired DNA:DNA and DNA:RNA duplexes, synthesis of various modifications that confer enhanced high-affinity recognit...
متن کاملIn vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides.
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 subu...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2000
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.97.10.5633