Antisense oligonucleotides gene expression

Antisense therapy means the selective, sequence-specific inhibition of gene expression by single-stranded DNA oligonucleotides. By hybridizing to the target mRNA, which results in a subsequent double-helix formation, gene expression is blocked. This process can occur at any point between the conclusion of transcription and initiation of translation or even possibly during translation. 

Monia BP, Lesnik EA, Gonzalez C, Lima WF, McGee D, Guinosso CJ, Kawasaki AM, Cook PD, Freier SM (1993) Evaluation of 2 -modified oligonucleotides containing 2 -deoxy gaps as antisense inhibitors of gene expression, J Biol Chem 268 14514-14522... 

Sopchik AE, Jiao X-Y, Bentrude WG (1999) Phosphorus, Sulfur and Silicon 144-146 373 Cohen JS (ed) (1989) Oligonucleotides, antisense inhibitors of gene expression. CRC, Boca Raton FI... 

Caruthers, M. H., Synthesis of oligonucleotides and oligonucleotide analogues, in Oligodeoxynucleotides — Antisense Inhibitors of Gene Expression, Cohen, J. S., Ed., CRC Press, Boca Raton, FL, 1989, 7. 

Often, it is desirable to block expression of particular genes that are activated by transcription factors. The anti-sense knockout experiments are directed toward this end and require the addition of an antisense oligonucleotide, which will anneal to the cis-acting regulatory element for a particular transcription factor in a specific gene. 

For gain-of-function mutations gene-blocking therapy, using antisense oligonucleotides or ribozymes to block gene expression... 

Particles from cationic lipids may also be useful for antisense therapy of skin disease — a nontoxic increase in the oligonucleotide uptake by cultivated keratinocytes and a sebocyte cell line has been reported [66]. Moreover, cationic dendri-mers also efficiently transfer reporter gene DNA to human keratinocytes cultivated in vitro. In the skin of hairless mice, in vivo transfection was possible with complexes, yet reporter gene expression was localized to perifollicular areas. Transfection, however, failed with the naked plasmid. For prolonged contact, biodegradable membranes coated with dendrimer/DNA complexes were used [67]. This hints at a follicular uptake of these complexes and indicates that gene transfection also may be possible with human skin, which has a thicker stratum comeum compared with mouse skin (eight to ten vs. two to three layers [58]). 

The zebrafish embryo is a very good model to investigate the role of a gene during development. Zebrafish embryos may be injected using various techniques to modulate gene expression such as knock down (morpholino antisense oligonucleotides), overexpression... 

Another group of researchers reported the first successful systemic selective inhibition of gene expression using antisense oligonucleotides. 

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