ASO-mediated exon skipping (SORL1)

ASO-mediated exon skipping (SORL1) is an investigational therapeutic approach that uses antisense oligonucleotides (ASOs), specifically splice-switching oligonucleotides (SSOs), to modulate the splicing of the SORL1 pre-mRNA. SORL1 encodes the sorting receptor SORLA, which plays a critical role in endosomal trafficking and prevents the amyloidogenic processing of amyloid precursor protein (APP). Pathogenic mutations in the complement-type repeat (CR) domains of SORLA (encoded by exons 23 to 33) cause protein misfolding, leading to loss-of-function or dominant-negative effects that drive Alzheimer's disease pathology. By targeting these specific exons, the ASOs induce exon skipping to exclude the mutated exon, resulting in the translation of an internally truncated but functional and non-toxic SORLA protein. This strategy aims to restore endosomal recycling and reduce amyloid-beta accumulation. The approach is being developed by researchers at Aarhus University for the treatment of Alzheimer's disease.

Other names

SORL1 exon-skipping ASOSORL-1 exon-skipping ASOSORL 1 exon-skipping ASOSORL1 splice-switching oligonucleotideSORL-1 splice-switching oligonucleotideSORL 1 splice-switching oligonucleotideSORL1 SSOSORL-1 SSOSORL 1 SSO