ArticlebioRxiv : the preprint server for biology2024
One-Size-Fits-Many: Antisense oligonucleotides for rescuing splicing mutations in hotspot exons.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Updated by
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations that impact splicing play a significant role in disease etiology but are not fully understood. To characterize the impact of exonic variants on splicing in 71 clinically-actionable disease genes in asymptomatic people, we analyzed 32,112 exonic mutations from ClinVar and Geisinger MyCode using a minigene reporter assay. We identify 1,733 splice-disrupting mutations, of which the most extreme 1-2% of variants are likely to be deleterious. We report that these variants are not distributed evenly across exons but are mostly concentrated in the ∼8% of exons that are most susceptible to splicing mutations (i.e. hotspot exons). We demonstrate that splicing defects in these exons can be reverted by ASOs targeting the splice sites of either their upstream or downstream flanking exons. This finding supports the feasibility of developing single therapeutic ASOs that could revert all splice-altering variants localized to a particular exon.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.