Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies

In vitro delivery of antisense oligonucleotides.

Oligonucleotides (ODNs) do not readily get access to their desired site (cytoplasm/nucleus) of action due to their high hydrophility and high molecular weight. Therefore enhancing components (carriers) are needed. Most widely used in vitro are cationic lipids (liposomes). Other systems include peptide conjugates or complexes, polymers and nanoparticles. We used cationic lipids and polymers, wit...

Mixed backbone antisense oligonucleotides: design, biochemical and biological properties of oligonucleotides containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments.

We have designed and synthesized mixed backbone oligonucleotides (MBOs) containing 2'-5'-ribo- and 3'-5'-deoxyribonucleotide segments. Thermal melting studies of the phosphodiester MBOs (three 2'-5'linkages at each end) with the complementary 3'-5'-DNA and -RNA target strands suggest that 2'-5'-ribonucleoside incorporation into 3'-5'-oligodeoxyribonucleotides reduces binding to the target stran...

Tritium Radiolabelled Antisense Oligonucleotides for ADME Studies

K. Webbley, S. Harris, J. Bloom, C. Henson, V. Wilson, C. Hawes, D. Price, J. Haffenden Pharmaron, Inc. Purpose Antisense Oligonucleotides (ASO), continue to elicit interest as novel therapeutic agents designed to specifically and selectively inhibit the production of various disease related gene products. For efficacy to occur, the therapeutic material must reach the site of action in quantiti...

Splice-switching antisense oligonucleotides as therapeutic drugs

Splice-switching oligonucleotides (SSOs) are short, synthetic, antisense, modified nucleic acids that base-pair with a pre-mRNA and disrupt the normal splicing repertoire of the transcript by blocking the RNA-RNA base-pairing or protein-RNA binding interactions that occur between components of the splicing machinery and the pre-mRNA. Splicing of pre-mRNA is required for the proper expression of...

Antisense Oligonucleotides Targeting Protein