title: Polyxylitol-based gene carrier improves the efficiency of gene transfer through enhanced endosomal osmolysis.
abstract: Endosomal escape is one of the important processes for efficient non-viral gene delivery. In this study, we synthesized a novel non-viral vector called polyxylitol-based gene carrier (XGC) through a Miachael addition reaction between xylitol diacrylate as a crosslinking agent and low molecular weight polyethylenimine (PEI 1.2kDa). The small amount of xylitol integrated into XGC (3.9% w/w) contributed 50% of the osmotic pressure of XGC, and enhaned the osmolysis of endosome cooperatively with the proton sponge effect, thus improving endosomal escape. Furthermore, XGC showed higher transfection efficiency in vivo in muscle tissue than pDNA alone or PEI 25kDa. In conclusion, our results show that XGC enhanced transfection efficiency compared with PEI 25kDa, the golden standard non-viral gene carrier, by enhancing endosomal escape without increasing the number of transfected cells.
  
  
  BACKGROUND
  Enhanced gene delivery methods would greatly facilitate the development of gene therapies. These authors demonstrate that a polyxylitol-based gene carrier enhanced the transfection efficiency compared with the gold standard non-viral gene carrier, as a result of enhancing endosomal escape without increasing the number of transfected cells, warranting further studies of this method.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Won-Seok
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Qiankun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Tae-Eun
authors.initials: TE
authors.lastname: Park
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Sang-Kee
authors.initials: SK
authors.lastname: Kang
authors.affiliation: National Institute of Animal Science, Rural Development Administration, Suwon, South Korea.
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea. Electronic address: chocs@plaza.snu.ac.kr.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea; Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, South Korea. Electronic address: cyjcow@snu.ac.kr.
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009997:Osmotic Pressure; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014993:Xylitol / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011094:Polyethyleneimine; D004247:DNA; D014993:Xylitol
keywords: Endosomal escape; Gene delivery; Osmolysis; Polyethylenimine; Proton sponge