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Protracted CLN3 Batten disease in mice that genetically model an exon-skipping therapeutic approach.
Centa, Jessica L; Stratton, Matthew P; Pratt, Melissa A; Osterlund Oltmanns, Jenna R; Wallace, Douglas G; Miller, Steven A; Weimer, Jill M; Hastings, Michelle L.
Afiliación
  • Centa JL; Center for Genetic Diseases, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
  • Stratton MP; Center for Genetic Diseases, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
  • Pratt MA; School of Graduate and Postdoctoral Studies, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
  • Osterlund Oltmanns JR; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USA.
  • Wallace DG; Department of Psychology, Northern Illinois University, DeKalb, IL 60115, USA.
  • Miller SA; Department of Psychology, Northern Illinois University, DeKalb, IL 60115, USA.
  • Weimer JM; Psychology Department, College of Health Professionals, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
  • Hastings ML; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD 57104, USA.
Mol Ther Nucleic Acids ; 33: 15-27, 2023 Sep 12.
Article en En | MEDLINE | ID: mdl-37359347
Genetic mutations that disrupt open reading frames and cause translation termination are frequent causes of human disease and are difficult to treat due to protein truncation and mRNA degradation by nonsense-mediated decay, leaving few options for traditional drug targeting. Splice-switching antisense oligonucleotides offer a potential therapeutic solution for diseases caused by disrupted open reading frames by inducing exon skipping to correct the open reading frame. We have recently reported on an exon-skipping antisense oligonucleotide that has a therapeutic effect in a mouse model of CLN3 Batten disease, a fatal pediatric lysosomal storage disease. To validate this therapeutic approach, we generated a mouse model that constitutively expresses the Cln3 spliced isoform induced by the antisense molecule. Behavioral and pathological analyses of these mice demonstrate a less severe phenotype compared with the CLN3 disease mouse model, providing evidence that antisense oligonucleotide-induced exon skipping can have therapeutic efficacy in treating CLN3 Batten disease. This model highlights how protein engineering through RNA splicing modulation can be an effective therapeutic approach.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Ther Nucleic Acids Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos