- Gene knockdown
: "For knockdowns in
combat sport s, seeKnockout ." For|the song|Knockdown (song)Gene knockdown refers to techniques by which the expression of one or more of an
organism 'sgene s is reduced, either through genetic modification (a change in theDNA of one of the organism'schromosome s) or by treatment with areagent such as a short DNA or RNAoligonucleotide with a sequence complementary to either an mRNA transcript or a gene. If genetic modification of DNA is done, the result is a "knockdown organism". If the change in gene expression is caused by an oligonucleotide binding to an mRNA or temporarily binding to a gene, this results in a temporary change in gene expression without modification of the chromosomal DNA and is referred to as a "transient knockdown".In a transient knockdown, the binding of this oligonucleotide to the active gene or its transcripts causes decreased expression through blocking of
transcription (in the case of gene-binding), degradation of themRNA transcript (e.g. by small interfering RNA (siRNA) orRNase -H dependent antisense) or blocking either mRNAtranslation , pre-mRNA splicing sites ornuclease cleavage sites used for maturation of other functional RNAs such asmiRNA cite journal | last = Summerton | first = J | year = 2007 | title = Morpholino, siRNA, and S-DNA Compared: Impact of Structure and Mechanism of Action on Off-Target Effects and Sequence Specificity | journal = Med Chem. | volume = 7 |issue = 7 | pages = 651–660 | url = http://www.ncbi.nlm.nih.gov/pubmed/17430206 | format =Pubmed ] (e.g. byMorpholino oligos or other RNase-H independent antisensecite journal | last = Summerton | first = J | year = 1999 | title = Morpholino Antisense Oligomers: The Case for an RNase-H Independent Structural Type | journal = Biochimica et Biophysica Acta | volume = 1489 | pages = 141–58 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10807004 | format =Pubmed ] ). The most direct use of transient knockdowns for learning about agene that has been sequenced, but has an unknown or incompletely known function, an experimental approach known asreverse genetics . Researchers draw inferences from how the knockdown differs from individuals in which the gene of interest is operational. Transient knockdowns are often used indevelopmental biology because oligos can be injected into single-celledzygotes and will be present in the daughter cells of the injected cell through embryonic development [cite journal | last = Nasevicius | first = A | coauthors = Ekker SC | year = 2000 | title = Effective targeted gene 'knockdown' in zebrafish | journal = Nature Genetics | volume = 26 | issue = 2 | pages = 216–20 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11017081 | format =Pubmed | doi = 10.1038/79951 ] .So far knockdown organisms with permanent alterations in their DNA have been engineered chiefly for research purposes. Also known simply as knockdowns, these organisms are most commonly used for reverse genetics, especially in species such as mice or rats for which transient knockdown technologies cannot easily be applied.
References
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Gene knockout
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