Lipid-Modified PEI Derivative-Based Binary/Ternary Polyplex Formulations for the Delivery of pDNA and mRNA in Primary Cells
Brief intro:
- Author: Amarnath Praphakar Rajendran, Luis Carlos Morales, Pavlo Michailo Tsisar, Bradley J. Kerr, Hasan Uluda?
- Journal: Biomacromolecules
- Publication Date: 2025 Mar 27
Abstract
A previous study has demonstrated the benefit of modification of polyethylenimine (PEI1.2k) by lipids through a p-hydroxyphenylacetic acid (PHPA) linker and polyanion (PA), which is now extended in this report to several primary cells. The formulated binary (lipopolymer/NAs) and ternary (lipopolymer/NAs/PA) complexes displayed no significant toxicity (MTT/hemolysis assay). The pDNA/mRNA complexes with PEI1.2k-PHPA-Lin9 and PEI1.2k-PHPA-Lau5-Ole5 lipopolymers showed gene expression levels higher than those of other lipopolymers. The transfection efficiencies of the ternary polyplexes of these lipopolymers possessed higher gene expression than those of the binary polyplexes. The serum-stable ternary polyplexes of PEI1.2k-PHPA-Lau5-Ole5 maintained high levels of mRNA expression in the lungs along with the spleen after intravenous injection. As in in vitro studies, transgene expression was relatively weak with binary complexes in muscle; however, a 10-fold higher efficiency was obtained with ternary complexes. Overall, our results provide improved gene formulations for the transfections of primary cells in vitro, as well as in in vivo animal models.
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