ArticleScientific reports2016
The intracellular trafficking mechanism of Lipofectamine-based transfection reagents and its implication for gene delivery.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 227 citations in OpenAlex.
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- RNA Delivery Using a Graphene Oxide-Polyethylenimine Hybrid Inhibiting Myotube Differentiation.ACS nanoscience Au · 2025Article
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- Transfection Technologies for Next-Generation Therapies.Journal of clinical medicine · 2025Review
- Electroporation- and Liposome-Mediated Co-Transfection of Single and Multiple Plasmids.Pharmaceutics · 2025Article
- Mechanistic intracellular PK/PD modeling to inform development strategies for small interfering RNA therapeutics.Molecular therapy. Nucleic acids · 2025Article
- Effective recognition of double-stranded RNA does not require activation of cellular inflammation.Science advances · 2025Article
- Combined replacement of lnc-MEG3 and miR-155 elicit tumor suppression in multiple myeloma.Epigenomics · 2025Article
- Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment.Current pharmaceutical biotechnology · 2025Review
- Induction of translation-suppressive G3BP1hLife · 2025Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipofectamine reagents are widely accepted as "gold-standard" for the safe delivery of exogenous DNA or RNA into cells. Despite this, a satisfactory mechanism-based explanation of their superior efficacy has remained mostly elusive thus far. Here we apply a straightforward combination of live cell imaging, single-particle tracking microscopy, and quantitative transfection-efficiency assays on live cells to unveil the intracellular trafficking mechanism of Lipofectamine/DNA complexes. We find that Lipofectamine, contrary to alternative formulations, is able to efficiently avoid active intracellular transport along microtubules, and the subsequent entrapment and degradation of the payload within acidic/digestive lysosomal compartments. This result is achieved by random Brownian motion of Lipofectamine-containing vesicles within the cytoplasm. We demonstrate here that Brownian diffusion is an efficient route for Lipofectamine/DNA complexes to avoid metabolic degradation, thus leading to optimal transfection. By contrast, active transport along microtubules results in DNA degradation and subsequent poor transfection. Intracellular trafficking, endosomal escape and lysosomal degradation appear therefore as highly interdependent phenomena, in such a way that they should be viewed as a single barrier on the route for efficient transfection. As a matter of fact, they should be evaluated in their entirety for the development of optimized non-viral gene delivery vectors.
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Registered trials
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