Patent ID: 8067569
Filing Date: 2011-11-29
Classification: A61K,A61P,C07F,C12N

Abstract:
1. An antisense morpholino oligomer containing between 12 and 40 morpholino subunits, wherein said subunits are (a1) linked together by either uncharged or positively charged, piperazine-containing phosphorodiamidate linkages, such that said uncharged phosphorodiamidate linkages are interspersed with at least two and up to half positively charged, piperazine-containing phosphorodiamidate linkages, and (a2) support a sequence of purine or pyrimidine base-pairing moieties, including a sequence between 12 and 25 nucleotide bases in length that is complementary to a target region of a selected preprocessed mRNA coding for a selected protein, where the 5′ end of the target region is 1-25 bases downstream of a normal splice acceptor site in said preprocessed mRNA, and having the properties that: (b1): the oligomer is taken up by eukaryotic cells; (b2): the oligomer hybridizes to the target region of preprocessed mRNA in such cells but does not hybridize to a splice acceptor junction, and (b3): the oligomer so hybridized to the target pre-mRNA prevents splicing at said normal acceptor splice site, such that the splice mechanism proceeds to a downstream splice acceptor site in the pre-mRNA, producing a splice variant processed mRNA with a truncated coding sequence.