Compositions and methods for modulation of LMNA expression

摘要

Disclosed herein are compounds, compositions and methods for modulating the expression of LMNA in a cell, tissue or animal. Also provided are methods of target validation. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Further provided are methods of identifying cis splicing regulatory elements of a selected mRNA using the disclosed compounds.

主权项

1. A method of modulating splicing of a LMNA pre-mRNA in a cell, comprising contacting the cell with a single-stranded antisense oligomeric compound comprising an oligonucleotide consisting of 12 to 30 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence comprising an at least 8 nucleobase portion complementary to an equal length portion of nucleotides 1983-2062 of SEQ ID NO: 4 and is at least 90% complementary to LMNA pre-mRNA having SEQ ID NO:4 as measured over the entirety of the oligonucleotide, wherein the oligonucleotide comprises at least one modified sugar moiety; and
thereby modulating splicing of the LMNA pre-mRNA in the cell, wherein the modulation of splicing results in an increase in the ratio of full-length LMNA mRNA to truncated LMNA mRNA.