ArticleProceedings of the National Academy of Sciences of the United States of America2005
Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 363 citations in OpenAlex.
- Advances in Polyethyleneimine-Derived Nanoformulations.Small science · 2026Review
- Contemporary Endothelial Genome Editing Technologies: Towards Precision Genetic Medicine for Vascular Diseases.International journal of molecular sciences · 2026Review
- An effective method to enhance transient gene expression by transfecting high-density CHO cells.AMB Express · 2025Article
- A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy.Science (New York, N.Y.) · 2025Article
- From genetic code to global health: the impact of nucleic acid vaccines on disease prevention and treatment.RSC medicinal chemistry · 2025Review
- Developing mRNA Nanomedicines with Advanced Targeting Functions.Nano-micro letters · 2025Review
- A review of the complex interplay between chemoresistance and lncRNAs in lung cancer.Journal of translational medicine · 2024Review
- Advances in non-viral mRNA delivery to the spleen.Biomaterials science · 2024Review
- Pharmacological Evaluation of Cannabinoid Receptor Modulators Using GRABInternational journal of molecular sciences · 2024Article
- Interaction of γ-Polyglutamic Acid/Polyethyleneimine/Plasmid DNA Ternary Complexes with Serum Components Plays a Crucial Role in Transfection in Mice.Pharmaceutics · 2024Article
- Design space determination to optimize DNA complexation and full capsid formation in transient rAAV manufacturing.Biotechnology and bioengineering · 2023Article
- 'Passive' nanoparticles for organ-selective systemic delivery: design, mechanism and perspective.Chemical Society reviews · 2023Review
- Polymer-Based mRNA Delivery Strategies for Advanced Therapies.Advanced healthcare materials · 2023Review
- O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules.Glycobiology · 2023Article
- Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications.Journal of translational medicine · 2022Review
- Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo.Science advances · 2022Article
- Hydrocephalus in mouse B3glct mutants is likely caused by defects in multiple B3GLCT substrates in ependymal cells and subcommissural organ.Glycobiology · 2021Article
- PEI fluorination reduces toxicity and promotes liver-targeted siRNA delivery.Drug delivery and translational research · 2021Article
- Genetic Delivery and Gene Therapy in Pulmonary Hypertension.International journal of molecular sciences · 2021Review
- Article
63 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
High-molecular-mass polyethylenimines (PEIs) are widely used vectors for nucleic acid delivery. We found that removal of the residual N-acyl moieties from commercial linear 25-kDa PEI enhanced its plasmid DNA delivery efficiency 21 times in vitro, as well as 10,000 times in mice with a concomitant 1,500-fold enhancement in lung specificity. Several additional linear PEIs were synthesized by acid-catalyzed hydrolysis of poly(2-ethyl-2-oxazoline), yielding the pure polycations. PEI87 and PEI217 exhibited the highest efficiency in vitro: 115-fold and 6-fold above those of the commercial and deacylated PEI25s, respectively; moreover, PEI87 delivered DNA to mouse lung as efficiently as the pure PEI25 but at a lower concentration and with a 200-fold lung specificity. These improvements stem from an increase in the number of protonatable nitrogens, which presumably results in a tighter condensation of plasmid DNA and a better endosomal escape of the PEI/DNA complexes. As a validation of the potential of such linear, fully deacylated PEIs in gene therapy for lung diseases, systemic delivery in mice of the complexes of a short interfering RNA (siRNA) against a model gene, firefly luciferase, and PEI25 or PEI87 afforded a 77% and 93% suppression of the gene expression in the lungs, respectively. Furthermore, a polyplex of a siRNA against the influenza viral nucleocapsid protein gene and PEI87 resulted in a 94% drop of virus titers in the lungs of influenza-infected animals.
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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.