A Potential New Therapeutic Approach for Friedreich Ataxia: Induction of Frataxin Expression With TALE Proteins

TALEs targeting a promoter sequence and fused with a transcription activation domain (TAD) may be used to specifically induce the expression of a gene as a potential treatment for haploinsufficiency. This potential therapeutic approach was applied to increase the expression of frataxin in fibroblast...

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Main Authors: Pierre Chapdelaine (Author), Zoé Coulombe (Author), Amina Chikh (Author), Catherine Gérard (Author), Jacques P Tremblay (Author)
Format: Book
Published: Elsevier, 2013-01-01T00:00:00Z.
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100 1 0 |a Pierre Chapdelaine  |e author 
700 1 0 |a Zoé Coulombe  |e author 
700 1 0 |a Amina Chikh  |e author 
700 1 0 |a Catherine Gérard  |e author 
700 1 0 |a Jacques P Tremblay  |e author 
245 0 0 |a A Potential New Therapeutic Approach for Friedreich Ataxia: Induction of Frataxin Expression With TALE Proteins 
260 |b Elsevier,   |c 2013-01-01T00:00:00Z. 
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500 |a 10.1038/mtna.2013.41 
520 |a TALEs targeting a promoter sequence and fused with a transcription activation domain (TAD) may be used to specifically induce the expression of a gene as a potential treatment for haploinsufficiency. This potential therapeutic approach was applied to increase the expression of frataxin in fibroblasts of Friedreich ataxia (FRDA) patients. FRDA fibroblast cells were nucleofected with a pCR3.1 expression vector coding for TALEFrat#8 fused with VP64. A twofold increase of the frataxin mRNA (detected by quantitative reverse transcription-PCR (qRT-PCR)) associated with a similar increase of the mature form of the frataxin protein was observed. The frataxin mRNA and protein were also increased by this TALE in the fibroblasts of the YG8R mouse model. The addition of 5-aza-2'-deoxycytidine (5-Aza-dC) or of valproic acid (VPA) to the TALE treatment did not produce significant improvement. Other TADs (i.e., p65, TFAP2α, SRF, SP1, and MyoD) fused with the TALEFrat#8 gene did not produce a significant increase in the frataxin protein. Thus the TALEFrat#8-VP64 recombinant protein targeting the frataxin promoter could eventually be used to increase the frataxin expression and alleviate the FRDA symptoms. 
546 |a EN 
690 |a Friedreich ataxia 
690 |a frataxin 
690 |a gene expression 
690 |a TAL effector 
690 |a transcription factor 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 2, Iss C (2013) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253116301779 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/afb32bc8f95b4e60af938a918e7fc410  |z Connect to this object online.