ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 71 citations in OpenAlex.
- Poly(ethylene Glycol) (PEG)-OligoRNA Hybridization to mRNA Enables Fine-Tuned Polyplex PEGylation for Spleen-Targeted mRNA Delivery.Small science · 2024Article
- mRNA vaccine designs for optimal adjuvanticity and delivery.RNA biology · 2024Review
- Matrices Activated with Messenger RNA.Journal of functional biomaterials · 2023Review
- Poly(aspartic acid)-Based Polymeric Nanoparticle for Local and Systemic mRNA Delivery.Molecular pharmaceutics · 2022Article
- Mechanisms and challenges of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Pulmonary siRNA delivery for lung disease: Review of recent progress and challenges.Journal of controlled release : official journal of the Controlled Release Society · 2021Review
- In Vitro and In Vivo Assessment of PEGylated PEI for Anti-IL-8/CxCL-1 siRNA Delivery to the Lungs.Nanomaterials (Basel, Switzerland) · 2020Article
- PEG-OligoRNA Hybridization of mRNA for Developing Sterically Stable Lipid Nanoparticles toward In Vivo Administration.Molecules (Basel, Switzerland) · 2019Article
- Scaffold-mediated delivery for non-viral mRNA vaccines.Gene therapy · 2018Article
- Negative regulation of cationic nanoparticle-induced inflammatory toxicity through the increased production of prostaglandin E2 via mitochondrial DNA-activated Ly6CTheranostics · 2018Article
- Microrna-26b attenuates monocrotaline-induced pulmonary vascular remodeling via targeting connective tissue growth factor (CTGF) and cyclin D1 (CCND1).Oncotarget · 2016Article
- Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying.Pharmaceutics · 2015Article
- Gene Transfection toward Spheroid Cells on Micropatterned Culture Plates for Genetically-modified Cell Transplantation.Journal of visualized experiments : JoVE · 2015Article
- Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells.Particle and fibre toxicology · 2015Article
- Polymeric Plerixafor: effect of PEGylation on CXCR4 antagonism, cancer cell invasion, and DNA transfection.Pharmaceutical research · 2014Article
- The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2014Article
- Article
- Gene transfection to spheroid culture system on micropatterned culture plate by polyplex nanomicelle: a novel platform of genetically-modified cell transplantation.Drug delivery and translational research · 2012Article
- Vectors for inhaled gene therapy in lung cancer. Application for nano oncology and safety of bio nanotechnology.International journal of molecular sciences · 2012Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Safety is a critical issue in clinical applications of nonviral gene delivery systems. Safe and effective gene introduction into the lungs was previously achieved using polyplexes from poly(ethyleneglycol) (PEG)-block-polycation [PEG-block-PAsp(DET)] and plasmid DNA (pDNA). Although PEGylated polyplexes appeared to be safe, an excess ratio of polycation to pDNA was needed to obtain sufficient transgene expression, which may cause toxicities shortly after gene introduction. In the present study, we investigated the combined use of two polymers, PEG-block-PAsp(DET) (B) and homo PAsp(DET) (H) across a range of mixing ratios to construct polyplexes. Although transgene expressions following in vitro transfections increased in parallel with increased proportions of H, polyplexes with B/H = 50/50 formulation produced the highest expression level following in vivo intratracheal administration. Higher proportions of H elicited high levels of cytokine induction with significant inflammation as assessed by histopathological examinations. Based on the aggregation behavior of polyplexes in bronchoalveolar lavage fluids (BALFs), we suggested that rapid aggregation of polyplexes in the lung induced acute inflammatory responses, resulting in reduced transgene expression. B/H formulation of polyplex can help to improve gene therapy for the respiratory system because it achieves both effective PEG shielding of polyplexes and functioning of PAsp(DET) polycations to enhance endosomal escape.
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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.