n-Lorem 2026 Nano-rare Patient Colloquium Poster Session

Wei Zhang, Ph.D. Associate Director, ASO Core Research, n-Lorem

Small non-coding RNAs are emerging as an important yet largely untapped class of disease-causing therapeutic targets. In this poster, we will describe how at n-Lorem, we have established an integrated discovery strategy to enable precision antisense oligonucleotide (ASO) therapeutics against pathogenic small RNAs, including spliceosomal small nuclear RNAs (snRNAs). Using RNU4-2 as a prototype, we combined mechanistic disease characterization, allele-selective ASO discovery, structural RNA analysis, endogenous RNA modification mapping, patient-derived cellular models, and functional splicing rescue to identify potent therapeutic candidates. This work demonstrated that mutant RNU4-2 acts through a toxic gain-of-function mechanism and that allele-selective ASOs can restore normal splicing in patient-derived cells. Beyond RNU4-2, this discovery pipeline establishes a broadly applicable strategy for targeting emerging small non-coding RNA disorders, creating new therapeutic opportunities for a rapidly expanding class of genetic diseases.