ArticlePharmaceutical research2004
Significant role of liver sinusoidal endothelial cells in hepatic uptake and degradation of naked plasmid DNA after intravenous injection.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 54 citations in OpenAlex.
- Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Smart micro/nanoneedles for gene delivery.Iranian journal of basic medical sciences · 2026Review
- Protocol for Isolation and Culture of Mouse Hepatocytes (HCs), Kupffer Cells (KCs), and Liver Sinusoidal Endothelial Cells (LSECs) in Analyses of Hepatic Drug Distribution.Methods in molecular biology (Clifton, N.J.) · 2022Article
- α-Galactosidase A Augmentation by Non-Viral Gene Therapy: Evaluation in Fabry Disease Mice.Pharmaceutics · 2021Article
- Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs.Pharmaceutics · 2021Review
- Sex, Age, and Bodyweight as Determinants of Extracellular DNA in the Plasma of Mice: A Cross-Sectional Study.International journal of molecular sciences · 2019Article
- PEG-Peptide Inhibition of Scavenger Receptor Uptake of Nanoparticles by the Liver.Molecular pharmaceutics · 2018Article
- Influence of DNA-Microbubble Coupling on Contrast Ultrasound-Mediated Gene Transfection in Muscle and Liver.Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography · 2016Article
- Structure-Activity Relationship of PEGylated Polylysine Peptides as Scavenger Receptor Inhibitors for Non-Viral Gene Delivery.Molecular pharmaceutics · 2015Article
- Article
- The uptake mechanism of PEGylated DNA polyplexes by the liver influences gene expression.Gene therapy · 2014Article
- Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades.Neuro-oncology · 2010Article
- Dysopsonin activity of serum DNA-binding proteins favorable for gene delivery.The Journal of pharmacology and experimental therapeutics · 2010Article
- Pharmacokinetic considerations regarding non-viral cancer gene therapy.Cancer science · 2008Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUptake and degradation of naked plasmid DNA (pDNA) by liver sinusoidal endothelial cells (LSECs) were investigated.
methodsTissue distribution and intrahepatic localization were determined after an intravenous injection of 111In- or 32P-labeled pDNA into rats. Cellular uptake and degradation of fluorescein- or 32P-labeled pDNA were evaluated using primary cultures of rat LSECs.
resultsFollowing intravenous injection, pDNA was rapidly eliminated from the circulation and taken up by the liver. Fractionation of liver-constituting cells by centrifugal elutriation revealed a major contribution of LSECs to the overall hepatic uptake of pDNA. Confocal microscopic study confirmed intracellular uptake of pDNA in cultured LSECs. Apparent cellular association of pDNA was similar at 37 degrees C and 4 degrees C. However, trichloroacetic acid (TCA) precipitation experiments showed the TCA-soluble radioactivity in the culture medium increased in an accumulative manner at 37 degrees C. Involvement of a specific mechanism was demonstrated, as the uptake of pDNA was significantly inhibited by excess unlabeled pDNA and some polyanions (polyinosinic acid, dextran sulfate, heparin) but not by others (polycytidylic acid, dextran). These inhibitors also reduced the amount of TCA-soluble radioactivity in the culture medium. CONCLUSION. These results suggest that LSECs efficiently ingested and rapidly degraded naked pDNA in vivo and in vitro and released the degradation products into the extracellular space.
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