ArticleNucleic acids research2020
Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Model selection in preclinical nucleic acid therapeutics research.Communications biology · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- New pharmacotherapies for the erythropoietic protoporphyrias: an analysis of trial protocols from a patient perspective.Orphanet journal of rare diseases · 2025Article
- NADScience advances · 2025Article
- Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.International journal of molecular sciences · 2025Review
- Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.Current issues in molecular biology · 2024Review
- Thiol-Specific Linkers for the Synthesis of Oligonucleotide Conjugates via Metal-Free Thiol-Ene Click Reaction.Bioconjugate chemistry · 2024Article
- Peptide Conjugates of a 2'-ACS omega · 2023Article
- Harnessing large language models (LLMs) for candidate gene prioritization and selection.Journal of translational medicine · 2023Article
- Introns and Their Therapeutic Applications in Biomedical Researches.Iranian journal of biotechnology · 2023Review
- Article
- Future directions for medicinal chemistry in the field of oligonucleotide therapeutics.RNA (New York, N.Y.) · 2023Article
- Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent β-thalassemia.American journal of hematology · 2022Article
- Analysis of Oligonucleotide Biodistribution and Metabolization in Experimental Animals.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Heme Biosynthetic Gene Expression Analysis With dPCR in Erythropoietic Protoporphyria Patients.Frontiers in physiology · 2022Article
- Efficient Synthesis of 2'-O-Methoxyethyl Oligonucleotide-Cationic Peptide Conjugates.ChemMedChem · 2021Article
- Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain-a patient-reported outcome efficacy measure.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Antisense Oligonucleotide-Mediated Exon-skipping Therapies: Precision Medicine Spreading from Duchenne Muscular Dystrophy.JMA journal · 2021Review
- The landscape and biological relevance of aberrant alternative splicing events in esophageal squamous cell carcinoma.Oncogene · 2021Article
- Efficient antisense inhibition reveals microRNA-155 to restrain a late-myeloid inflammatory programme in primary human phagocytes.RNA biology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietic protoporphyria (EPP) is a rare genetic disease in which patients experience acute phototoxic reactions after sunlight exposure. It is caused by a deficiency in ferrochelatase (FECH) in the heme biosynthesis pathway. Most patients exhibit a loss-of-function mutation in trans to an allele bearing a SNP that favors aberrant splicing of transcripts. One viable strategy for EPP is to deploy splice-switching oligonucleotides (SSOs) to increase FECH synthesis, whereby an increase of a few percent would provide therapeutic benefit. However, successful application of SSOs in bone marrow cells is not described. Here, we show that SSOs comprising methoxyethyl-chemistry increase FECH levels in cells. We conjugated one SSO to three prototypical targeting groups and administered them to a mouse model of EPP in order to study their biodistribution, their metabolic stability and their FECH splice-switching ability. The SSOs exhibited distinct distribution profiles, with increased accumulation in liver, kidney, bone marrow and lung. However, they also underwent substantial metabolism, mainly at their linker groups. An SSO bearing a cholesteryl group increased levels of correctly spliced FECH transcript by 80% in the bone marrow. The results provide a promising approach to treat EPP and other disorders originating from splicing dysregulation in the bone marrow.
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