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.

Polybrene是一种季铵盐,最早作为肝素中和剂被引入临床^[1],此外,低剂量的Polybrene在体内和体外均被广泛用于提高病毒介导的基因转移效率^[2-5]。Polybrene通过中和对立双分子层之间的静电斥力来促进病毒在细胞表面的结合^[6-7]。

Polybrene(0 ~ 32 µg/mL;24h)呈浓度依赖性。从低至4 µg/mL的浓度开始,出现明显的神经炎珠,而8 µg/mL的浓度则引起神经炎碎片^[8]。Polybrene (8µg/mL)显著降低间充质干细胞(Mesenchymal stem cells, MSCs)的增殖率^[9]。在多种细胞系中,Polybrene可显著提高脂质感染的效率,并补偿血清介导的脂质感染抑制^[10]。

Polybrene (4 µg/µL；ICV)注射后第3天小鼠出现运动功能障碍。并且Polybrene可以诱导小鼠神经死亡和神经胶质瘤^[8]。