Oligonucleotide analogues targeting human lmna
AssigneesSarepta Therapeutics, Inc., The Progeria Research Foundation, Inc., The United States of America, as represented by the Secretary, Dept. of Health and Human Services, University of Maryland
InventorsMichael R. Erdos, Francis S. Collins, Kan Cao, Ryszard Kole, Richard Keith Bestwick, Leslie B. Gordon
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Abstract
Provided are LMNA-targeted antisense oligonucleotides for reducing expression of one or more aberrantly spliced LMNA mRNA isoforms that encode progerin.
Claims20
An antisense oligomer compound of formula (I):
- or a pharmaceutically acceptable salt thereof,
- where each Nu is a nucleobase which taken together forms a targeting sequence;
- T is selected from:
- and
- G is a cell penetrating peptide (“CPP”) and linker moiety selected from:
- —C(O)CH2NH—CPP—Ra, and
- wherein the CPP is attached to the linker moiety by an amide bond at the CPP carboxy terminus, Ra is attached to the CPP amino terminus by an amide bond wherein Ra is selected from H, acetyl, benzoyl, and stearoyl, and the CPP is selected from SEQ ID NOS:
- 5-21, and
- wherein the targeting sequence is selected from:
- a)
- SEQ ID NO:
- 3
- (CTGAGCCGCTGGCAGATGCCTTGTC)
- wherein Z is 23;
- and
- b)
- SEQ ID NO:
- 4
- (GAGGAGATGGGTCCACCCACCTGGG)
- wherein
- Z is 23.
An antisense oligomer compound of formula (III):
- or a pharmaceutically acceptable salt thereof, wherein:
- each Nu is a nucleobase which taken together form a targeting sequence (5′ to 3′) selected from:
- a) SEQ ID NO:
- 3 (CTGAGCCGCTGGCAGATGCCTTGTC) wherein Z is 23;
- and
- b) SEQ ID NO:
- 4 (GAGGAGATGGGTCCACCCACCTGGG) wherein Z is 23.
An antisense oligomer compound, or a pharmaceutically acceptable salt thereof, selected from:
An antisense oligomer compound, or a pharmaceutically acceptable salt thereof, selected from:
Dependencies are inferred from the claim text.