Therapeutic targeting of a long non-coding RNA

Antisense oligonucleotides (ASOs) against the long non-coding RNA UBE3A antisense transcript (UBE3A-ATS) could represent a feasible therapy for the monogenic disorder Angelman syndrome, a new study reports. The disease results from loss of expression of the maternal UBE3A allele in the presence of the imprinted (that is, silenced) paternal allele. Meng et al. were able to activate expression of the paternal Ube3a allele in cultured mouse neurons and in live mice by specifically targeting the silencing Ube3a-ATS with ASOs. Restoration of UBE3A protein in a mouse model of Angelman syndrome was sufficient to ameliorate cognitive deficits. Given that genomic organization and regulation at the imprinting control centre is highly conserved between mice and humans, the researchers posit that their findings highlight a viable therapeutic strategy in humans.