National Yang Ming Chiao Tung University

Leland Stanford Junior University

Tzu-Han Wang

Stanley N Cohen

Tzu-Hao Cheng

Chia-Rung Liu

Chia-Rung Lu

Aspects of the invention include methods of selectively reducing the deleterious activity of mutant extended trinucleotide repeat containing genes in a cell, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended trinucleotide repeat containing gene may be selectively reduced in a variety of different ways, e.g., by selectively decreasing SPT4 mediated transcriptional activity, by enhancing functionality of proteins encoded thereby, etc. Aspects of the invention further include assays for identifying agents that find use in methods of the invention, e.g. as summarized above. Methods and compositions of the invention find use in a variety of different applications, including the prevention or treatment of disease conditions associated with the presence of genes containing mutant extended trinucleotide repeats, such as Huntington's Disease (HD).

Selective reduction of the deleterious activity of extended tri-nucleotide repeat containing genes

This invention provides a method for modulating the expression of a first gene in a cell wherein the first gene is one containing more than 36 CAG trinucleotide repeats and encoding a protein that form polyglutamine-mediated protein aggregation. Suppression of the first gene is achieved by reducing the expression of SPT4 gene or SUPT4H gene. It can also be achieved by inhibiting the formation of a Spt4/Spt5 complex or a Supt4h/Supt5h complex. Also provided is a method for identifying an agent useful for modulating the expression and aggregation of CAG-expanded gene product, or treating a polyglutamine disease such as Huntington's disease.

Methods for identifying agents useful for modulating the expression and aggregation of CAG-expanded gene product in cells

Methods for modulating the expression and aggregation of a CAG-expanded gene product in cells and methods for identifying agents useful for doing the same

Methods for modulating the expression and aggregation of CAG-expanded gene product in cells and methods for identifying agents useful for doing the same

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Taipei, Taiwan

Tzu-Han Wang