发明名称 |
MULTIMERIC OLIGONUCLEOTIDES COMPOUNDS |
摘要 |
The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided. |
申请公布号 |
US2015299695(A1) |
申请公布日期 |
2015.10.22 |
申请号 |
US201214344523 |
申请日期 |
2012.09.14 |
申请人 |
Uhlmann Eugen;Weber Markus;Subramanian Romesh;Rockel Thomas Dino;Krieg Arthur M. |
发明人 |
Uhlmann Eugen;Weber Markus;Subramanian Romesh;Rockel Thomas Dino;Krieg Arthur M. |
分类号 |
C12N15/113 |
主分类号 |
C12N15/113 |
代理机构 |
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代理人 |
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主权项 |
1. A compound comprising the general formula: X-L-[X-L]i-X,
wherein i is an integer from 0 to 9, the value of which indicates the number of units of [X-L]i present in the compound, wherein each X is independently a targeting oligonucleotide of 8 to 50 nucleotides in length having a region of complementarity comprising at least 7 contiguous nucleotides complementary to a target region of a genomic target sequence, and each L is a linker that links at least two Xs and that is more susceptible to cleavage in a mammalian extract than each X, wherein when i=0, and wherein the general formula is 5′X3′-L-5′X3′ and when the target regions complementary to the first X and second X do not overlap in the genomic target sequence, the 5′-end of the target region complementary to the first X and the 3′-end of the target region complementary to the second X are not within a distance of 0 to 4 nucleotides in the genomic target sequence, and wherein at least one L does not comprise an oligonucleotide having a self-complementary nucleotide sequence, and wherein at least one L does not comprise an oligonucleotide having a nucleotide sequence that is complementary to a region of the genomic target sequence that is contiguous with the target regions complementary to two immediately flanking Xs. |
地址 |
Glashutten DE |