RNA interference for the treatment of gain-of-function disorders
AssigneeUniversity of Massachusetts
InventorsNeil Aronin, Phillip D. Zamore
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Abstract
The present invention relates to the discovery of an effective treatment for a variety of gain-of-function diseases, in particular, Huntington's disease (HD). The present invention utilizes RNA Interference technology (RNAi) against polymorphic regions in the genes encoding various gain-of-function mutant proteins resulting in an effective treatment for the gain-of-function disease.
Claims12
A composition for treating a subject having or at risk for Huntington's disease caused by a mutation within the htt gene encoding a gain-of-function mutant huntingtin protein, comprising:
- a vector that expresses an effective amount of an siRNA or an shRNA targeting a non-disease causing heterozygous single nucleotide polymorphism (SNP) within a gene encoding said mutant huntingtin protein located at a site distinct from the expanded CAG region mutation within the htt gene encoding the mutant huntingtin protein.
A composition for treating a subject having or at risk for Huntington's disease caused by a mutation within the htt gene encoding a gain-of-function mutant huntingtin protein, comprising a vector that expresses an effective amount of a siRNA or shRNA targeting a heterozygous SNP within a gene encoding said mutant huntingtin protein, wherein the SNP has an allelic frequency of at least 10% in a sample population and is present at a genomic site selected from the group consisting of RS362331, RS4690077, RS363125, RS363075, RS362268, RS362267, RS362307, RS362306, RS362305, RS362304, and RS362303.
A composition for treating a subject having or at risk for Huntington's disease characterized or caused by a mutant huntingtin (htt) protein, comprising a vector that expresses an effective amount of a siRNA targeting a heterozygous single nucleotide polymorphism (SNP) within a gene encoding the mutant htt protein, such that RNA silencing of said gene occurs, wherein the siRNA comprises
- (i) an antisense strand or a variant thereof having sufficient complementarity to the SNP at genomic site RS362307 to direct target-specific RNA interference of the gene encoding the mutant htt protein;
- and
- (ii) a sense strand or a variant thereof that is substantially complementary to the antisense strand, such that the sense and antisense strands are capable of annealing together.
A composition for treating a subject having or at risk for Huntington's disease characterized or caused by a mutant huntingtin (htt) protein, comprising a vector that expresses an effective amount of a siRNA targeting a heterozygous single nucleotide polymorphism (SNP) within a gene encoding the mutant htt protein, such that RNA silencing of said gene occurs, wherein the siRNA comprises
- (i) an antisense strand or a variant thereof having sufficient complementarity to the SNP at genomic site RS362331 or RS363125 to direct target-specific RNA interference of the gene encoding the mutant htt protein;
- and
- (ii) a sense strand or a variant thereof that is substantially complementary to the antisense strand, such that the sense and antisense strands are capable of annealing together.
Dependencies are inferred from the claim text.