Journal ArticleDOI
Morpholino antisense oligomers: the case for an RNase H-independent structural type.
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TLDR
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.About:
This article is published in Biochimica et Biophysica Acta.The article was published on 1999-12-10. It has received 689 citations till now. The article focuses on the topics: RNase P & RNase H.read more
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Journal ArticleDOI
Effective targeted gene ‘knockdown’ in zebrafish
TL;DR: It is shown here that antisense, morpholino-modified oligonucleotides (morpholinos) are effective and specific translational inhibitors in zebrafish, and conserved vertebrate processes and diseases are now amenable to a systematic, in vivo, reverse-genetic paradigm using zebra fish embryos.
Journal ArticleDOI
RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform
C. Frank Bennett,Eric E. Swayze +1 more
TL;DR: The molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligon nucleotides behave in the body are focused on.
Journal ArticleDOI
p53 Activation by Knockdown Technologies
Mara E. Robu,Jon D. Larson,Aidas Nasevicius,Aidas Nasevicius,Soraya Beiraghi,Charles Brenner,Steven A. Farber,Stephen C. Ekker +7 more
TL;DR: It is shown here that MO off-targeting results in induction of a p53-dependent cell death pathway, and p53 inhibition could potentially be applicable to other systems to suppress off- target effects caused by other knockdown technologies.
Journal ArticleDOI
Controlling morpholino experiments: don't stop making antisense
Judith S. Eisen,James C. Smith +1 more
TL;DR: It is discussed how the use of morpholinos can lead to misleading results, including off-target effects, and controls that will allow researchers to interpret morpholino experiments correctly are suggested.
Journal ArticleDOI
Morpholino oligos: making sense of antisense?
TL;DR: The evidence so far suggests that, with careful controls, morpholinos provide a relatively simple and rapid method to study gene function.
References
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Journal ArticleDOI
Site and mechanism of antisense inhibition by C-5 propyne oligonucleotides.
Courtney Moulds,Jason Lewis,Brian C. Froehler,Deborah Grant,Teresa Huang,John F. Milligan,Mark D. Matteucci,Richard Wagner +7 more
TL;DR: C-5 propyne 2'-deoxy phosphorothioate ONs, once hybridized to RNA, are completely effective at preventing mRNA translation, and it is predicted that the development of more effective ONs will only come from modifications which increase the rate of ON/RNA complex formation within the nucleus.
Journal ArticleDOI
Cellular penetration and antisense activity by a phenoxazine-substituted heptanucleotide.
TL;DR: The unique permeation properties and gene-specific antisense activity of the 7-mer phenoxazine/C-5 propynyl U S-ON paves the way for developing potent, cost-effective, self-permeable antisense therapeutics.
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Nuclear delivery of antisense oligodeoxynucleotides through reversible permeabilization of human leukemia cells with streptolysin O
David G. Spiller,D M Tidd +1 more
TL;DR: This work has directly confirmed the conclusion suggested by reported antisense effects, that streptolysin O reversibly permeabilizes the plasma membrane toward oligonucleotides and may be utilized to effect biochemical "microinjection" of these molecules directly into the cytoplasm.
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Prediction of antisense oligonucleotide efficacy by in vitro methods
Olga V. Matveeva,Brice Felden,Alexander Tsodikov,Joseph F. Johnston,Brett P. Monia,John F. Atkins,Raymond F. Gesteland,Susan M. Freier +7 more
TL;DR: If complicated mRNA structures with internal base pairings are responsible for the problem, then a rapid, inexpensive, and reliable in vitro method for the prediction of accessible mRNA regions would be valuable and allow efficient targeting by complementary oligonucleotides and could increase the speed of antisense drug discovery.
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In vitro efficacy of morpholino-modified antisense oligomers directed against tumor necrosis factor-alpha mRNA.
TL;DR: A panel of morpholino antisense oligomers (M-AS) for their ability to inhibit macrophage tumor necrosis factor-α (TNF-α) release was evaluated and phosphodiester and phosphorothioate types of oligonucleotides were compared.