ArticleScientific reports2023
High spontaneous integration rates of end-modified linear DNAs upon mammalian cell transfection.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
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- Synthetic messenger RNA vaccines and transcriptomic dysregulation: Evidence from new-onset adverse events and cancers post-vaccination.World journal of experimental medicine · 2025Article
- Preventing secondary primary malignancies (SPMs) in CAR-T cell therapy through site-specific transgene integration into genomic safe harbors (GSHs).Journal of translational medicine · 2025Review
- The knock-in atlas: a web resource for targeted protein trap by CRISPR/Cas9 in human and mouse cell lines.Nucleic acids research · 2025Article
- Application of Gene Editing Technology Based on Targeted Delivery Materials in TNBC.ACS omega · 2025Review
- A review of synergistic strategies in cancer therapy: resveratrol-loaded hydrogels for targeted and multimodal treatment.Discover oncology · 2025Review
- Vector-Free Deep Tissue Targeting of DNA/RNA Therapeutics via Single Capacitive Discharge Conductivity-Clamped Gene Electrotransfer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The 60-year evolution of lipid nanoparticles for nucleic acid delivery.Nature reviews. Drug discovery · 2024Review
- Determinants of minor satellite RNA function in chromosome segregation in mouse embryonic stem cells.The Journal of cell biology · 2024Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In gene therapy, potential integration of therapeutic transgene into host cell genomes is a serious risk that can lead to insertional mutagenesis and tumorigenesis. Viral vectors are often used as the gene delivery vehicle, but they are prone to undergoing integration events. More recently, non-viral delivery of linear DNAs having modified geometry such as closed-end linear duplex DNA (CELiD) have shown promise as an alternative, due to prolonged transgene expression and less cytotoxicity. However, whether modified-end linear DNAs can also provide a safe, non-integrating gene transfer remains unanswered. Herein, we compare the genomic integration frequency upon transfection of cells with expression vectors in the forms of circular plasmid, unmodified linear DNA, CELiDs with thioester loops, and Streptavidin-conjugated blocked-end linear DNA. All of the forms of linear DNA resulted in a high fraction of the cells being stably transfected-between 10 and 20% of the initially transfected cells. These results indicate that blocking the ends of linear DNA is insufficient to prevent integration.
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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.