AAV-delivered exon-skipping vector shows preclinical promise for NF1 mutation
A bioRxiv preprint describes an AAV-U7-SnRNA approach to skip exon 17 of the NF1 gene, with AAV-F capsid outperforming AAV-9 and AAV-B1 in biodistribution and exon-skipping efficiency in humanised mouse models.
Researchers have published a preprint on bioRxiv describing preclinical work aimed at advancing exon-skipping therapy for Neurofibromatosis type 1 (NF1), a condition caused by loss-of-function variants in the NF1 gene encoding neurofibromin. The study focuses on NF1 exon 17, where specific pathogenic mutations could theoretically be addressed by inducing the cell's splicing machinery to skip the affected exon and restore a partially functional reading frame.
The team developed antisense oligonucleotides (ASOs) targeting NF1 exon 17 and packaged them within a U7-SnRNA expression cassette delivered by three adeno-associated virus (AAV) capsids — AAV-9, AAV-F, and AAV-B1. A reporter cassette linking luciferase and eGFP via a T2A peptide enabled direct tracking of vector biodistribution and exon-skipping activity in vivo using humanised mouse models.
Among the capsids tested, AAV-F demonstrated superior biodistribution and exon-skipping efficacy compared with AAV-9 and AAV-B1. The authors frame these findings as a step towards in vivo testing and eventual clinical translation, though the work remains at the preclinical stage and has not yet been peer-reviewed. NF1 affects approximately 1 in 3,000 individuals and is associated with tumour predisposition, neurodevelopmental features, and variable expressivity; mutation-specific therapeutic strategies of this kind represent an active area of research.
Plain-language version
For patients, families, and general readers. Educational only — not medical advice.
Neurofibromatosis type 1 (NF1) is a genetic condition caused by changes in a gene called NF1. It can cause growths on nerves, skin changes, and other health effects. Researchers have published early-stage laboratory results describing a new approach to treating a specific type of NF1 mutation. The method uses a specially engineered virus to deliver instructions that tell cells to skip over the faulty section of the NF1 gene, potentially allowing the gene to produce a more functional protein.
The experiments were carried out in mice that had been given human versions of the gene, not in people. Three different viral delivery vehicles were tested, and one — called AAV-F — worked better than the others at getting the instructions into cells and producing the desired effect.
This is very early-stage research. It has not yet been reviewed by independent scientists, and there is no approved therapy based on this approach. Researchers say it is a step towards eventual trials in people, but that will require further testing.
This is an educational summary, not medical advice. If anything here raises questions for you, please speak with your GP or a clinical professional.
Sources
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-07-02Preclinical translation of Neurofibromatosis type 1 (NF1) exon 17 skipping using targeted U7-SnRNA packaged into engineered AAV serotypes.