ArticleGene therapy2003
Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord.
Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Intrathecal drug delivery in the era of nanomedicine.Advanced drug delivery reviews · 2020Pooled it
- Unraveling the role of MAG, PTEN, and NOTCH1 in axonal regeneration: a network analysis and molecular dynamics study of siRNA/drugs/nanocarriers interactions.Journal of translational medicine · 2025Article
- Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair.Journal of nanobiotechnology · 2024Review
- Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound.Nanomaterials (Basel, Switzerland) · 2024Article
- Biomaterial-based gene therapy.MedComm · 2023Review
- Defined Human Leukemic CD34+ Liquid Cultures to Study HDAC/Transcriptional Repressor Complexes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- AKAP150 and its Palmitoylation Contributed to Pain Hypersensitivity Via Facilitating Synaptic Incorporation of GluA1-Containing AMPA Receptor in Spinal Dorsal Horn.Molecular neurobiology · 2021Article
- Bio-nano interactions: binding proteins, polysaccharides, lipids and nucleic acids onto magnetic nanoparticles.Biomaterials research · 2021Review
- Biomimicking Fiber Scaffold as an Effective In Vitro and In Vivo MicroRNA Screening Platform for Directing Tissue Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- The Configuration of the Perivascular System Transporting Macromolecules in the CNS.Frontiers in neuroscience · 2019Article
- In vivo methods for acute modulation of gene expression in the central nervous system.Progress in neurobiology · 2018Review
- Article
- Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection.Scientific reports · 2016Article
- The therapeutic potential of interleukin-10 in neuroimmune diseases.Neuropharmacology · 2015Review
- Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene.Gene therapy · 2013Article
- Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS.Molecular pharmaceutics · 2013Review
- Targeted delivery of self-complementary adeno-associated virus serotype 9 to the brain, using magnetic resonance imaging-guided focused ultrasound.Human gene therapy · 2012Article
- Gene therapy for the treatment of chronic peripheral nervous system pain.Neurobiology of disease · 2012Review
- Non-viral gene therapy for spinal cord regeneration.Drug discovery today · 2012Review
- Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain.Molecular pain · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene delivery into the spinal cord provides a potential approach to the treatment of spinal cord traumatic injury, amyotrophic lateral sclerosis, and spinal muscular atrophy. These disorders progress over long periods of time, necessitating a stable expression of functional genes at therapeutic levels for months or years. We investigated in this study the feasibility of achieving prolonged transgene expression in the rat spinal cord through repeated intrathecal administration of plasmid DNA complexed with 25 kDa polyethylenimine (PEI) into the lumbar subarachnoid space. With a single injection, DNA/PEI complexes could provide transgene expression in the spinal cord 40-fold higher than naked plasmid DNA. The transgene expression at the initial level persisted for about 5 days, with a low-level expression being detectable for at least 8 weeks. When repeated dosing was tested, a 70% attenuation of gene expression was observed following reinjection at a 2-week interval. This attenuation was associated with apoptotic cell death and detected even using complexes containing a noncoding DNA that did not mediate any gene expression. When each component of the complexes, PEI polymer or naked DNA alone, were tested in the first dosing, no reduction was found. Using polyethylene glycol (PEG)-grafted PEI for DNA complexes, no attenuation of gene expression was detected after repeated intrathecal injections, even in those rats receiving three doses, administered 2 weeks apart. Lumbar puncture is a routine and relatively nontraumatic clinical procedure. Repeated administration of DNA complexed with PEG-grafted PEI through this less invasive route may prolong the time span of transgene expression when needed, providing a viable strategy for the gene therapy of spinal cord disorders.
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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.