Abstract：
:We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpectedly, we found that ASOs with 2'-deoxy-2'-fluoro (2'-F) nucleotides, but not with other 2' chemical modifications, have an additional property: they form heteroduplexes with RNA that are specifically recognized by the interleukin enhancer-binding factor 2 and 3 complex (ILF2/3). 2'-F ASO-directed recruitment of ILF2/3 to RNA can be harnessed to control gene expression by modulating alternative splicing of target transcripts. ILF2/3 recruitment to precursor mRNA near an exon results in omission of the exon from the mature mRNA, both in cell culture and in mice. We discuss the possibility of using chemically engineered ASOs that recruit specific proteins to modulate gene expression for therapeutic intervention.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Rigo F,Hua Y,Chun SJ,Prakash TP,Krainer AR,Bennett CFdoi
10.1038/nchembio.939subject
Has Abstractpub_date
2012-04-15 00:00:00pages
555-61issue
6eissn
1552-4450issn
1552-4469pii
nchembio.939journal_volume
8pub_type
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