From N-of-1 to versatility in propionic acidemia: Antisense oligonucleotide-mediated skipping of a constitutive PCCA pseudoexon
. ASO treatment successfully restored enzymatic activity, particularly in fibroblast lines, with residual activity exceeding 1% of normal. These findings suggest that ASO-mediated splicing correction targeting the 84-bp pseudoexon can restore mRNA, protein, and enzymatic function in individuals with deep intronic mutations, as well as in other individuals with propionic acidemia, indicating the feasibility of ASO therapy as a molecular treatment strategy for a subset of individuals with propionic acidemia.
Authors
- Yasuko Mikami-Saito
- Jun Takayama (ORCID: https://orcid.org/0000-0003-2803-6526)
- Osamu Ohara (ORCID: https://orcid.org/0000-0002-3328-9571)
- Eriko Totsune
- Atsuo Kikuchi (ORCID: https://orcid.org/0000-0003-1002-8739)
- Yoichi Wada Yoichi Wada
- Yoko Nakajima
- Natsuko Arai-Ichinoi
- Naoya Saijo
- Shigeo Kure
- Yasuhiro Maeda
Institutions
- Fujita Health University (JP)
- Tohoku University (JP)
- Miyagi Children's Hospital (JP)
- RIKEN Center for Advanced Intelligence Project (JP)
- Tohoku Medical Megabank Organization (JP)
- Kazusa DNA Research Institute (JP)
Publication Details
- Journal
- Molecular Therapy — Nucleic Acids
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1016/j.omtn.2026.102925
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Astellas Pharma
- Tohoku University