Patent ID: 8008271

Claim:
A method of inhibiting expression of a human SOD1 gain-of-function target mRNA, and providing for expression of a RNAi resistant replacement gene in a cell comprising administering to the cell a nucleic acid agent comprising a first polynucleotide sequence encoding an RNAi agent specific for the human SOD1 gain-of-function target mRNA, and a second polynucleotide sequence encoding a RNAi resistant replacement gene, wherein the RNAi agent comprises an antisense strand having sufficient sequence complementarity to the human SOD1 gain-of-function target mRNA to induce cleavage of the target mRNA, and a sense strand complementary to said antisense strand, and wherein the RNAi replacement gene comprises a nucleotide sequence encoding human SOD1 and wherein the RNAi replacement gene comprises SEQ ID NO:3 or SEQ ID NO:85, whereby expression of the human SOD1 gain-of-function target mRNA is inhibited and expression of the RNAi resistant replacement gene is achieved.