Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing.

@article{citeulike:654214, abstract = {Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended ("off-target") silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially complementary transcripts by all siRNAs tested. Silencing of perfectly matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2'-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position dependence of 2'-O-methyl ribosyl modification contrasts with the broader position dependence of base-pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts.}, address = {1Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck \& Co., Inc., Seattle, Washington 98109, USA.}, author = {Jackson, Aimee L L. and Burchard, Julja and Leake, Devin and Reynolds, Angela and Schelter, Janell and Guo, Jie and Johnson, Jason M M. and Lim, Lee and Karpilow, Jon and Nichols, Kim and Marshall, William and Khvorova, Anastasia and Linsley, Peter S S. }, citeulike-article-id = {654214}, doi = {10.1261/rna.30706}, issn = {1355-8382}, journal = {RNA}, keywords = {off-target, rnai}, month = {May}, posted-at = {2008-05-01 09:05:08}, priority = {2}, title = {Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing.}, url = {http://dx.doi.org/10.1261/rna.30706}, year = {2006} }

TY - JOUR ID - citeulike:654214 L3 - citeulike-article-id:654214 TI - Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. JF - RNA AD - 1Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co., Inc., Seattle, Washington 98109, USA. SN - 1355-8382 N2 - Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended ("off-target") silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially complementary transcripts by all siRNAs tested. Silencing of perfectly matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2'-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position dependence of 2'-O-methyl ribosyl modification contrasts with the broader position dependence of base-pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts. KW - off-target KW - rnai AU - Jackson, Aimee L AU - Burchard, Julja AU - Leake, Devin AU - Reynolds, Angela AU - Schelter, Janell AU - Guo, Jie AU - Johnson, Jason M AU - Lim, Lee AU - Karpilow, Jon AU - Nichols, Kim AU - Marshall, William AU - Khvorova, Anastasia AU - Linsley, Peter S PY - 2006/05/08/ UR - http://dx.doi.org/10.1261/rna.30706 ER -