Chemical modification and design of anti-miRNA oligonucleotides.
Summary of "Chemical modification and design of anti-miRNA oligonucleotides."
Antisense techniques have been employed for over 30 years to suppress expression of target RNAs. Recently, microRNAs (miRNAs) have emerged as a new class of small, non-coding, regulatory RNA molecules that widely impact gene regulation, differentiation and disease states in both plants and animals. Antisense techniques that employ synthetic oligonucleotides have been used to study miRNA function and some of these compounds may have potential as novel drug candidates to intervene in diseases where miRNAs contribute to the underlying pathophysiology. Anti-miRNA oligonucleotides (AMOs) appear to work primarily through a steric blocking mechanism of action; these compounds are synthetic reverse complements that tightly bind and inactivate the miRNA. A variety of chemical modifications can be used to improve the performance and potency of AMOs. In general, modifications that confer nuclease stability and increase binding affinity improve AMO performance. Chemical modifications and/or certain structural features of the AMO may also facilitate invasion into the miRNA-induced silencing complex. In particular, it is essential that the AMO binds with high affinity to the miRNA 'seed region', which spans bases 2-8 from the 5'-end of the miRNA.Gene Therapy advance online publication, 14 July 2011; doi:10.1038/gt.2011.100.
Affiliation
Molecular Genetics and Biophysics, Integrated DNA Technologies, Coralville, IA, USA.
Journal Details
This article was published in the following journal.
Name: Gene therapy
ISSN: 1476-5462
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21753793
- DOI: http://dx.doi.org/10.1038/gt.2011.100
Medical and Biotech [MESH] Definitions
Phosphorothioate Oligonucleotides
Modified oligonucleotides in which one of the oxygens of the phosphate group is replaced with a sulfur atom.
Green Chemistry Technology
Pollution prevention through the design of effective chemical products that have low or no toxicity and use of chemical processes that reduce or eliminate the use and generation of hazardous substances.
Drug Design
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Gene Knockdown Techniques
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Evolution, Chemical
Chemical and physical transformation of the biogenic elements from their nucleosynthesis in stars to their incorporation and subsequent modification in planetary bodies and terrestrial biochemistry. It includes the mechanism of incorporation of biogenic elements into complex molecules and molecular systems, leading up to the origin of life.
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