ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 121 citations in OpenAlex.
- Epigenetic regulation of transgenes.Journal of biotechnology · 2026Review
- Mechanisms and Strategies for Enhancing DNA Nuclear Entry in Gene Delivery.Cellular and molecular bioengineering · 2026Article
- Minicircle DNA Vaccines: Overcoming Delivery and Expression Barriers in Next-Generation Immunization.Vaccines · 2026Review
- DNA Cut-Ligation Cyclization Surpasses Jacobson-Stockmayer J-Factor Expectations by over Threefold.Biomolecules · 2026Article
- A low-toxicity circular single-stranded DNA platform for safe and potent IL-12 immunotherapy against hepatocellular carcinoma.Journal of nanobiotechnology · 2026Article
- Anticodon-edited transfer RNAs (ACE-tRNAs) encoded as therapeutic nonviral minimal DNA vectors.Nucleic acids research · 2026Article
- Plasmid2MC: efficient cell-free generation of high-purity minicircle DNA for genome editing in mammalian cells.Communications biology · 2025Article
- Precision therapeutic tRNA rescue of nonsense mutation R166X inJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
- Anticodon Edited Transfer RNAs (ACE-tRNAs) Encoded as Therapeutic Nonviral Minimal DNA Vectors.bioRxiv : the preprint server for biology · 2025Article
- Article
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.BMC genomics · 2024Article
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.bioRxiv : the preprint server for biology · 2024Article
- Review
- Live attenuated-nonpathogenicFrontiers in microbiology · 2024Review
- The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner.Nature communications · 2023Article
- A Review of CRISPR Tools for Treating Usher Syndrome: Applicability, Safety, Efficiency, and In Vivo Delivery.International journal of molecular sciences · 2023Review
- A Tet-Inducible CRISPR Platform for High-Fidelity Editing of Human Pluripotent Stem Cells.Genes · 2022Article
- Minicircle Delivery to the Neural Retina as a Gene Therapy Approach.International journal of molecular sciences · 2022Review
- Therapeutic effect of multiple functional minicircle vector encoding anti-CD25/IL-10/CXCR3 in allograft rejection model.The Korean journal of internal medicine · 2022Article
- A brief review on DNA vaccines in the era of COVID-19.Future virology · 2021Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Current efforts in nonviral gene therapy are plagued by a pervasive difficulty in sustaining therapeutic levels of delivered transgenes. Minicircles (plasmid derivatives with the same expression cassette but lacking a bacterial backbone) show sustained expression and hold promise for therapeutic use where persistent transgene expression is required. To characterize the widely-observed silencing process affecting expression of foreign DNA in mammals, we used a system in which mouse liver presented with either plasmid or minicircle consistently silences plasmid but not minicircle expression. We found that preferential silencing of plasmid DNA occurs at a nuclear stage that precedes transport of mRNA to the cytoplasm, evident from a consistent >25-fold minicircle/plasmid transcript difference observed in both nuclear and total RNA. Among possible mechanisms of nuclear silencing, our data favor chromatin-linked transcriptional blockage rather than targeted degradation, aberrant processing, or compromised mRNA transport. In particular, we observe dramatic enrichment of H3K27 trimethylation on plasmid sequences. Also, it appears that Pol II can engage the modified plasmid chromatin, potentially in a manner that is not productive in the synthesis of high levels of new transcript. We outline a scenario in which sustained differences at the chromatin level cooperate to determine the activity of foreign DNA.
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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.