Polybrene

Polybrene, a quaternary ammonium salt, was firstly introduced into clinical practice as a heparin neutralizer^[1]. Besides, polybrene at lower doses was popularly used to promote the efficiency of virus-mediated gene transfer both in vivo and in vitro^[2-5]. Polybrene promote the binding of viruses on the cell surface by neutralizing the electrostatic repulsion between the opposing bilayers^[6-7].

Polybrene(0-32 µg/mL;24h) displays concentration-dependent effects. Starting at concentrations as low as 4 µg/mL, distinct neuritic beads emerge, whereas a concentration of 8 µg/mL induces neuritic fragmentation^[8]. Polyethylene(8µg/mL) significantly reduced the proliferation rate of Mesenchymal stem cells (MSCs) ^[9]. Polybrene markedly enhances the efficiency of lipofection and also compensates the serum-mediated inhibition of lipofection in a variety of cell lines^[10].

Polybrene(4 µg/µL；ICV) injection resulted in mice exhibiting motor dysfunction on the third day.Polybrene induces neural death and gliosis in mice^[8].

References:
[1]. Weiss.W. A, Gilman, J. S, et,al. Heparin neutralization with polybrene administered intravenously. J. Am. Med. Assoc. 166, 603-607 (1958).
[2]. Davis, H. E., Morgan, J. R. et,al. Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes. Biophys. Chem. 97, 159-172 (2002).
[3]. Bellodi-Privato, M. et al. AAV gene transfer to the retina does not protect retrovirally transduced hepatocytes from the immune response. J. Mol. Med (Berl.). 82, 403-410 (2004).
[4]. Lauwers, E. et al. Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein. Brain Pathol. 13, 364-372 (2003).
[5]. Ferry, N., Duplessis, O., et,al. Retroviral-mediated gene transfer into hepatocytes in vivo. Proc. Natl Acad. Sci. USA 88, 8377-8381 (1991).
[6]. Sinn, P. L., Sauter, S. L. et,al. Gene therapy progress and prospects: development of improved lentiviral and retroviral vectors--design, biosafety, and production. Gene Ther. 12, 1089-1098 (2005).
[7]. Kafri, T. Lentivirus vectors: difficulties and hopes before clinical trials. Curr. Opin. Mol. Ther. 3, 316-326 (2001).
[8]. Bao F, Shi H, et,al. Polybrene induces neural degeneration by bidirectional Ca2+ influx-dependent mitochondrial and ER-mitochondrial dynamics. Cell Death Dis. 2018 Sep 20;9(10):966. doi: 10.1038/s41419-018-1009-8. PMID: 30237514; PMCID: PMC6148003.
[9].Lin P, Correa D, et,al. Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction. PLoS One. 2011;6(8):e23891. doi: 10.1371/journal.pone.0023891. Epub 2011 Aug 26. PMID: 21887340; PMCID: PMC3162604.
[10].Abe A, Miyanohara A, Friedmann T. Polybrene increases the efficiency of gene transfer by lipofection. Gene Ther. 1998 May;5(5):708-11. doi: 10.1038/sj.gt.3300652. PMID: 9797877.