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METHODS OF DESIGNING SHORT HAIRPIN RNAS (SHRNAS) FOR GENE SILENCING

机译:设计用于基因沉默的短发RNA(SHRNA)的方法

摘要

The invention relates to methods and apparatuses and computer program products for classifying siRNA functional sequence motifs for use in an shRNA core sequence, and for designing shRNA, shRNA core sequences or sense strand sequences thereof or antisense sequences thereof. The shRNA core sequence comprises an antisense strand sequence and a sense strand sequence and is designed to produce an siRNA for silencing a target gene in a cell. In one embodiment, the method selects a first plurality of siRNA functional sequence motifs each with a predicted silencing efficacy against a targeted sequence motif within a transcript of a target gene that is equal or greater than a chosen threshold of silencing efficacy, and classifies each siRNA functional sequence motif in the first plurality of siRNA functional sequence motifs as belonging to a first class of siRNA functional sequence motifs when the siRNA functional sequence motif has a 3 ' terminal nucleotide that is a cytosine, or as belonging to a second class of siRNA functional sequence motifs when said siRNA functional sequence motif does not have a 3 ' terminal nucleotide that is a cytosine. The invention further discloses methods of designing by replacing the 3 ' terminal non-cytosine nucleotide with a cytosine or by adding a 3 ' terminal cytosine to an siRNA functional sequence motif.
机译:本发明涉及用于对在shRNA核心序列中使用的siRNA功能序列基序进行分类以及用于设计shRNA,shRNA核心序列或其有义链序列或其反义序列的方法,装置和计算机程序产品。 shRNA核心序列包含反义链序列和有义链序列,设计用于产生用于沉默细胞中靶基因的siRNA。在一个实施方案中,该方法选择第一多个siRNA功能序列基序,每个基序对靶基因的转录物中的靶序列基序具有等于或大于选择的沉默效果阈值的预测的沉默功效,并对每个siRNA进行分类。当第一多个siRNA功能序列基序具有作为胞嘧啶的3'末端核苷酸时属于第一类siRNA功能序列基序,或者属于第二类siRNA功能序列基序当所述siRNA功能序列基序不具有胞嘧啶的3'末端核苷酸时,该序列基序。本发明进一步公开了通过用胞嘧啶替换3'末端非胞嘧啶核苷酸或通过向siRNA功能序列基序添加3'末端胞嘧啶的设计方法。

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