Abstract: [Problems] To provide a chemically modified siRNA that has improved stability against RNase enzymes and selectively exhibits silencing of FUS P525L mutation which is a causative gene of ALS. [Solution] Provided is a chemically modified siRNA comprising a sense strand and an antisense strand, or a salt thereof, wherein: the antisense strand includes a complementary or substantially complementary region in a portion of a mRNA that codes FUS P525L mutation protein; the complementary region has a nucleotide length of 19 to 21; and the siRNA contains at least one substitution selected from the group consisting of a 2?-F-nucleotide, a 2?-OMe-nucleotide, a nucleotide in which a 2?-O atom and a 4?-O atom are bridged by methylene, a 2?-deoxynucleotide, and a phosphorothioate bond that forms an internucleotide bond.

Abstract: The present invention provides siRNA which selectively exhibits silencing of FUS P525L mutation, pharmaceutical compositions comprising the siRNA and therapeutic uses of ALS, as well as methods for screening the ALS therapeutic agents.