Show Notes
Cheerie D et al., The American Journal of Human Genetics - This episode summarizes the N1C VARIANT consensus guidelines (version 1.0) that define a framework to evaluate pathogenic DNA variants for eligibility for antisense oligonucleotide (ASO) approaches, and describes the supporting tools, videos, and piloting process developed by the N¼1 Collaborative. Key terms: antisense oligonucleotides, variant eligibility, N1C VARIANT, splice correction, exon skipping.
Study Highlights:
An international working group developed the N1C VARIANT guidelines to assess variant amenability to ASO strategies including splice correction, exon skipping, transcript knockdown, and upregulation of the wild-type allele. The guidelines use a five-tier classification scheme: eligible, likely eligible, unlikely eligible, not eligible, and unable to assess. Development included iterative piloting with multidisciplinary volunteer assessors, training videos, and an interactive eligibility calculator. The guidelines and resources are intended for clinicians, laboratories, and researchers prioritizing candidates for individualized ASO development.
Conclusion:
The N1C VARIANT guidelines provide a practical, consensus-based framework, training materials, and an eligibility calculator to systematically assess pathogenic variants for ASO therapies, with planned yearly updates to reflect advances in the field.
QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-04-18.
Scope: article metadata and core scientific claims from the narration, excluding analogies, intro/outro, and music.
Factual QC score: 10/10.
Metadata QC score: 10/10.
Supported core claims: 8.
Claims flagged for review: 0.
Metadata checks passed: 4.
Metadata issues found: 0.
QC result: Pass.
Music:
Enjoy the music based on this article at the end of the episode.
Article title:
Consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments
First author:
Cheerie D
Journal:
The American Journal of Human Genetics
DOI:
10.1016/j.ajhg.2025.02.017
Reference:
Cheerie D, Meserve MM, Beijer D, et al. Consensus guidelines for assessing eligibility of pathogenic DNA variants for antisense oligonucleotide treatments. Am J Hum Genet. 2025;112:975-983. doi:10.1016/j.ajhg.2025.02.017
License:
http://creativecommons.org/licenses/by/4.0/
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Episode link: https://basebybase.com/episodes/targeting-the-genome-guidelines-for-antisense-oligonucleotide-therapy-eligibility
