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FARAFARA Cure FA

Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)n Repeats by PNA or LNA Targeting

Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich's ataxia. (GAA)n expansions form specific molecular structures, and are associated with epigenetic modifications. With the aim of interfering with such DNA structures within pathological (GAA)n expansions, we examined sequence-specific interaction of peptide nucleic acid (PNA) with (GAA)n repeats of different lengths (short: n=9, medium: n=75 or long: n=115) by chemical probing. They found that different DNA structures were formed with GAA repeats of different lengths. Furthermore, they showed that some PNA's abolished the DNA structures by binding to the DNA. Locked nucleic acid (LNA) oligonucleotides also inhibited the triplex formation at GAA repeat expansion. Thus, by inhibiting disease related higher order DNA structures in the Frataxin gene, such PNA and LNA oligomers may have potential for discovery of drugs aiming at recovering Frataxin expression.

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About the Author

Jen Farmer

Jen Farmer

Executive Director

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