ArticleNature medicine2025
In vivo base editing extends lifespan of a humanized mouse model of prion disease.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Article
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.PLoS pathogens · 2026Article
- StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.Molecular brain · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Cytosine base editing of LPA in transgenic mice averts large deletions.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression.Genome medicine · 2026Article
- The octapeptide repeats of prion protein play critical roles in the pathogenesis of prion diseases.Acta neuropathologica communications · 2026Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Review
- Genome-wide screens identify core regulators of cell surface prion protein expression.Scientific reports · 2026Article
- Review
- AAV-PHP.eB Peripheral Delivery and Central Expression in Cre Mice.The Journal of comparative neurology · 2026Article
- Oligosaccharyltransferase (OST) complex inhibition effectively treats rodent and human prions.PLoS pathogens · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
27 authors.
Funding
Abstract
Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain. Systemic injection of dual-adeno-associated virus PHP.eB encoding BE3.9max and single guide RNA installing PRNP R37X resulted in 37% average installation of the desired edit, 50% reduction of PrP in the mouse brain and 52% extension of lifespan in transgenic human PRNP mice inoculated with pathogenic human prion isolates representing the most common sporadic and genetic subtypes of prion disease. We further engineered base editing systems to achieve improved in vivo potency and reduced base editor expression in nontargeting tissues, resulting in 63% average PrP reduction in the mouse brain from a 6.7-fold lower viral dose, with no detected off-target editing of anticipated clinical significance observed in either human cells or mouse tissues. These findings support the potential of in vivo base editing as one-time treatment for prion disease.
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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.