Малые интерферирующие РНК: различия между версиями

 
=== Побочные эффекты ===
Сбой цели --- это еще одна трудность при использовании миРНК как инструмента для достидения нокдауна генов. Гены с неполной комплементарностью блокируются миРНК (т. е. фаутически миРНК действует как микроРНК), что приводит к трудностям в интерпретации результатов опытов и сожержит риск токсичности. Однако, этого можно избежать, организуя соответствующие контрольные опыты, и создавая алгоритмы конструирования миРНК, которые приводят к миРНК, не дающим сбоев цели.
Off-targeting is another challenge to the use of siRNAs as a gene knockdown tool. Here, genes with incomplete complementarity are inadvertently downregulated by the siRNA (effectively, the siRNA acts as a miRNA), leading to problems in data interpretation and potential 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-basepair-long stretches from position 2 onward in the siRNA matching with 3’UTR regions in off-targeted genes.<ref>{{cite journal |author=Birmingham A, Anderson E, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y, Baskerville S, Maksimova E, Robinson K, Karpilow J, Marshall W, Khvorova A |title=3' UTR seed matches, but not overall identity, are associated with RNAi off-targets |journal=Nat Methods |volume=3 |issue=3 |pages=199–204 |year=2006 |doi= 10.1038/nmeth854 |pmid=16489337}}</ref>
Затем можно проанализировать экспрессию генов по всему геному, например, при помощи метода микромассивов ({{lang: англ.|microarray technology}}), чтобы проверить отсутствие сбоев цели и поизвести дальнейшую настройку алгиритмов. В работе 2006 года,
Off-targeting is another challenge to the use of siRNAs as a gene knockdown tool. Here, genes with incomplete complementarity are inadvertently downregulated by the siRNA (effectively, the siRNA acts as a miRNA), leading to problems in data interpretation and potential 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-basepair-long stretches from position 2 onward in the siRNA matching with 3’UTR regions in off-targeted genes.<ref>{{cite journal |author=Birmingham A, Anderson E, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y, Baskerville S, Maksimova E, Robinson K, Karpilow J, Marshall W, Khvorova A |title=3' UTR seed matches, but not overall identity, are associated with RNAi off-targets |journal=Nat Methods |volume=3 |issue=3 |pages=199–204 |year=2006 |doi= 10.1038/nmeth854 |pmid=16489337}}</ref>
 
== Перспективы применения в терапии ==