Systemic Delivery of DNA or siRNA Mediated by Linear Polyethylenimine (L-PEI) Does Not Induce an Inflammatory Response |
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Authors: | Marie-Elise Bonnet Patrick Erbacher Anne-Laure Bolcato-Bellemin |
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Institution: | (1) Polyplus-transfection SA, Bioparc, BP90018, Boulevard Sébastien Brandt, 67401 Illkirch Cedex, France |
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Abstract: | Purpose The success of nucleic acid therapies depends upon delivery vehicle’s ability to selectively and efficiently deliver therapeutic
nucleic acids to target organ with minimal toxicity. The cationic polymer polyethylenimine (PEI) has been widely used for
nucleic acid delivery due to its versatility and efficiency. In particular, the last generation of linear PEI (L-PEI) is being
more efficient in vivo than the first generation of branched PEI. This led to several clinical trials including phase II bladder cancer therapy
and human immunodeficiency virus immunotherapy. When moving towards to the clinic, it is crucial to identify potential side-effects
induced by the delivery vehicle.
Materials and Methods For this purpose we have analyzed the production of pro-inflammatory cytokines tumor necrosis factor-α, interferon (IFN)-γ,
interleukin (IL)-6, IL-12/IL-23, IFN-β and IL-1β] and hepatic enzyme levels (alanine aminotransferase, aspartate aminotransferase,
lactate dehydrogenase and alkaline phosphatase) in the blood serum of mice after systemic injection of DNA or siRNAs delivered
with L-PEI.
Results Our data show no major production of pro-inflammatory cytokines or hepatic enzymes after injection of DNA or oligonucleotides
active for RNA interference (siRNAs or sticky siRNAs) complexed with L-PEI. Only a slight induction of IFN-γ was measured
after DNA delivery, which is probably induced by the CpG mediated response.
Conclusion Taken together our data highlight that linear polyethylenimine is a delivery reagent of choice for nucleic acid therapeutics.
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Keywords: | hepatic enzyme polyethylenimine pro-inflammatory cytokine siRNA/DNA delivery sticky siRNAs (ssiRNAs) |
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