ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Nanoparticle-mediated rhodopsin cDNA but not intron-containing DNA delivery causes transgene silencing in a rhodopsin knockout model.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Innovative approaches to treatment of eye diseases: advances in stem cell therapy use in ophthalmology.International ophthalmology · 2025Review
- Gene augmentation for autosomal dominant retinitis pigmentosa using rhodopsin genomic loci nanoparticles in the P23HGene therapy · 2023Article
- Innovative Strategies for Drug Delivery to the Ocular Posterior Segment.Pharmaceutics · 2023Review
- Prospects of Non-Coding Elements in Genomic DNA Based Gene Therapy.Current gene therapy · 2022Review
- Gene Therapy for Rhodopsin-associated Autosomal Dominant Retinitis Pigmentosa.International ophthalmology clinics · 2021Article
- The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases.International journal of molecular sciences · 2021Review
- Hepatocyte nuclear factor 4α negatively regulates connective tissue growth factor during liver regeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Rhodopsin Genomic Loci DNA Nanoparticles Improve Expression and Rescue of Retinal Degeneration in a Model for Retinitis Pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- A cerium oxide loaded glycol chitosan nano-system for the treatment of dry eye disease.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Genomic form of rhodopsin DNA nanoparticles rescued autosomal dominant Retinitis pigmentosa in the P23H knock-in mouse model.Biomaterials · 2018Article
- DNA nanoparticles are safe and nontoxic in non-human primate eyes.International journal of nanomedicine · 2018Article
- Injectable hydrogels for ophthalmic applications.Journal of controlled release : official journal of the Controlled Release Society · 2017Review
- Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.Journal of controlled release : official journal of the Controlled Release Society · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Previously, we compared the efficacy of nanoparticle (NP)-mediated intron-containing rhodopsin (sgRho) vs. intronless cDNA in ameliorating retinal disease phenotypes in a rhodopsin knockout (RKO) mouse model of retinitis pigmentosa. We showed that NP-mediated sgRho delivery achieved long-term expression and phenotypic improvement in RKO mice, but not NP housing cDNA. However, the protein level of the NP-sgRho construct was only 5-10% of wild-type at 8 mo postinjection. To have a better understanding of the reduced levels of long-term expression of the vectors, in the present study, we evaluated the epigenetic changes of subretinal delivering NP-cDNA vs. NP-sgRho in the RKO mouse eyes. Following the administration, DNA methylation and histone status of specific regions (bacteria plasmid backbone, promoter, rhodopsin gene, and scaffold/matrix attachment region) of the vectors were evaluated at various time points. We documented that epigenetic transgene silencing occurred in vector-mediated gene transfer, which were caused by the plasmid backbone and the cDNA of the transgene, but not the intron-containing transgene. No toxicity or inflammation was found in the treated eyes. Our results suggest that cDNA of the rhodopsin transgene and bacteria backbone interfered with the host defense mechanism of DNA methylation-mediated transgene silencing through heterochromatin-associated modifications.
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Registered trials
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.