Extracellular vesicles-mediated delivery of SpCas9 RNPs for therapeutic gene editing in Spinocerebellar Ataxia Type 3 - PubMed
4 hours ago
- #Gene editing
- #CRISPR-Cas9
- #Extracellular vesicles
- Spinocerebellar Ataxia Type 3 (SCA3) is caused by CAG tract overexpansion in the ATXN3 gene.
- CRISPR-Cas9 gene editing is a potential therapeutic strategy for SCA3 but faces delivery challenges.
- Extracellular vesicles (EVs) are used to deliver SpCas9 and sgRNA ribonucleoproteins for safer gene editing.
- A palmitoylation motif enables SpCas9 and sgRNA enrichment into EVs.
- A photocleavable linker (PhoCl) allows photo-inducible release of SpCas9, improving ATXN3 targeting in vitro.
- EVs loaded with SpCas9 ribonucleoproteins achieved ATXN3 knockout in SCA3 patient-derived iPSCs and animal models.
- This method offers a transient delivery approach for gene editing tools, promising for genetic disease treatment.