Morpholino antisense oligomers: the case for an RNase H-independent structural type.
RNase H-competent phosphorothioates (S-DNAs) have dominated the antisense field in large part because they offer reasonable resistance to nucleases, they afford good efficacy in cell-free test systems, they can be targeted against sites throughout the RNA transcript of a gene, and they are widely available from commercial sources at modest prices. However, these merits are counterbalanced by significant limitations, including: degradation by nucleases, poor in-cell targeting predictability, low sequence specificity, and a variety of non-antisense activities. In cell-free and cultured-cell systems where one wishes to block the translation of a messenger RNA coding for a normal protein, RNase H-independent morpholino antisense oligos provide complete resistance to nucleases, generally good targeting predictability, generally high in-cell efficacy, excellent sequence specificity, and very preliminary results suggest they may exhibit little non-antisense activity.
Summerton
J
J
Gene Tools, Corvallis, OR 97339, USA. mail@gene-tools.com
D017398:Alternative Splicing / Q000187:drug effects; D002474:Cell-Free System / Q000201:enzymology; D004337:Drug Carriers / Q000737:chemistry; D015195:Drug Design; D015870:Gene Expression / Q000187:drug effects; D018390:Gene Targeting / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D009025:Morpholines / Q000737:chemistry*; D009693:Nucleic Acid Hybridization / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D016914:Ribonuclease H / Q000378:metabolism*; D013379:Substrate Specificity; D013873:Thionucleotides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology
D004337:Drug Carriers; D009025:Morpholines; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D016914:Ribonuclease H