Short interfering RNA: differenze tra le versioni

Versione delle 18:45, 3 ago 2006

Versione delle 20:24, 3 ago 2006

Riga 15:

==Specificità degli siRNA==

La RNAi si interseca con diversi altri processi cellulari. Non è dunque sorprendente che l'introduzione di siRNA nella cellula possa indurre alcuni effetti non specifici. Una cellula di [[mammifero]], ad esempio, può ''interpretare'' una molecola di RNAds come un composto di origine [[virus|virale]], avviando una risposta [[sistema immunitario|immunitaria]]. Inoltre, dal momento che i [[miRNA|microRNA]] (molecole prodotte dalla cellula per regolare l'[[espressione genica]]) sono estremamente simili come struttura ai siRNA, sono possibili indesiderate interferenze anche con questo ''pathway''.

<!--RNAi intersects with a number of other pathways, so it is not surprising that on occasion non-specific effects are triggered by the experimental introduction of an siRNA. When a mammalian cell encounters a double-stranded RNA such as an siRNA, it may mistake it as a viral by-product and mount an immune response. Furthermore, since structurally related [[miRNA|microRNAs]] modulate gene expression largely via incomplete complementarity with a target [[mRNA]], unintended off-targeting may be effected by the introduction of an siRNA.

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===Immunità innata===

Introduction of too much siRNA can result in non-specific events due to activation of innate immune responses. Most papers suggest that this is probably due to activation of the dsRNA sensor PKR, although retinoic acid inducible Gene I (RIG-I) may also be involved. One promising method of reducing the non-specific effects is to convert the siRNA into a [[miRNA|microRNA]]. MicroRNAs occur naturally, and by harnessing this endogenous pathway it should be possible to achieve similar gene knockdown at comparatively low concentrations of resulting siRNAs. This should minimise non-specific effects.

===Off-targeting===

Off-targeting is another challenge facing siRNAs as a gene knockdown tool. Here, genes with incomplete complementarity are inadvertently downregulated by the siRNA (effectively, the siRNA acts as an [[miRNA]]), leading to problems in data interpretation and potentially toxicity. This however can be partly addressed by designing appropriate control experiments, and siRNA design algorithms are currently being developed to produce siRNAs free from off-targeting. Genome-wide expression analysis, e.g. by microarray technology, can then be used to verify this and further refine the algorithms. A 2006 paper from the laboratory of Dr Khvorova implicates 6 or 7 basepairs long stretches from position 2 onwards in the siRNA matching with 3'UTR regions in off-targeting genes.-->

==Prospettive future==