Difficulties translating antisense-mediated activation of Frataxin expression from cell culture to mice

Audrius Kilikevicius, Jun Wang, Xiulong Shen, Frank Rigo, Thahza P. Prakash, Marek Napierala & David R. Corey (2022); RNA Biology, 19:1, 364-372, DOI: 10.1080/15476286.2022.2043650 

 In this study, we investigate the potential for oligonucleotides to increase frataxin expression in a mouse model for FA. After confirming successful in vivo delivery of oligonucleotides using a benchmark gapmer targeting the nuclear noncoding RNA Malat1, we tested anti-FXN oligonucleotides designed to function by various mechanisms. None of these strategies yielded enhanced expression of FXN in the model mice. Our inability to translate activation of FXN expression from cell culture to mice may be due to inadequate potency of our compounds or differences in the molecular mechanisms governing FXN gene repression and activation in FA model mice.

Difficulties translating antisense-mediated activation of Frataxin expression from cell culture to mice