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Effective gene therapy of Stargardt disease with PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles.
Sun, Da; Sun, Wenyu; Gao, Song-Qi; Lehrer, Jonathan; Naderi, Amirreza; Wei, Cheng; Lee, Sangjoon; Schilb, Andrew L; Scheidt, Josef; Hall, Ryan C; Traboulsi, Elias I; Palczewski, Krzysztof; Lu, Zheng-Rong.
Afiliación
  • Sun D; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Sun W; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Gao SQ; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Lehrer J; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Naderi A; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Wei C; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Lee S; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Schilb AL; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Scheidt J; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Hall RC; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • Traboulsi EI; Department of Pediatric Ophthalmology and Center for Genetic Eye Diseases, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44106, USA.
  • Palczewski K; Gavin Herbert Eye Institute, Department of Ophthalmology, Departments of Physiology and Biophysics, Chemistry, and Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697, USA.
  • Lu ZR; Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Mol Ther Nucleic Acids ; 29: 823-835, 2022 Sep 13.
Article en En | MEDLINE | ID: mdl-36159595
ABSTRACT
Stargardt disease (STGD) is the most common form of inherited retinal genetic disorders and is often caused by mutations in ABCA4. Gene therapy has the promise to effectively treat monogenic retinal disorders. However, clinically approved adeno-associated virus (AAV) vectors do not have a loading capacity for large genes, such as ABCA4. Self-assembly nanoparticles composed of (1-aminoethyl)iminobis[N-(oleoylcysteinyl-1-amino-ethyl)propionamide (ECO; a multifunctional pH-sensitive/ionizable amino lipid) and plasmid DNA produce gene transfection comparable with or better than the AAV2 capsid. Stable PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles produce specific and prolonged expression of ABCA4 in the photoreceptors of Abca4 -/- mice and significantly inhibit accumulation of toxic A2E in the eye. Multiple subretinal injections enhance gene expression and therapeutic efficacy with an approximately 69% reduction in A2E accumulation in Abca4 -/- mice after 3 doses. Very mild inflammation was observed after multiple injections of the nanoparticles. PEG-ECO/pGRK1-ABCA4-S/MAR nanoparticles are a promising non-viral mediated gene therapy modality for STGD type 1 (STGD1).
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Texto completo: 1 Colección: 01-internacional Idioma: En Revista: Mol Ther Nucleic Acids Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Idioma: En Revista: Mol Ther Nucleic Acids Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos