title: Highly Branched Poly(β-amino esters) for Non-Viral Gene Delivery: High Transfection Efficiency and Low Toxicity Achieved by Increasing Molecular Weight.
abstract: A successful polymeric gene delivery vector is denoted by both transfection efficiency and biocompatibility. However, the existing vectors with combined high efficacy and minimal toxicity still fall short. The most widely used polyethylene imine (PEI), polyamidoamine (PAMAM) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) suffer from the correlation: either too toxic or little effective. Here, we demonstrate that with highly branched poly(β-amino esters) (HPAEs), a type of recently developed gene delivery vector, the high gene transfection efficiency and low cytotoxicity can be achieved simultaneously at high molecular weight (MW). The interactions of HPAE/DNA polyplexes with cell membrane account for the favorable correlation between molecular weight and biocompatibility. In addition to the effect of molecular weight, the molecular configuration of linear and branched segments in HPAEs is also pivotal to endow high transfection efficiency and low cytotoxicity. These findings provide renewed perspective for the further development of clinically viable gene delivery vectors.
authors.affiliation: Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.|Institute of Biomedical Engineering, National Taiwan University , Taipei, Taiwan , 100, R.O.C.
authors.forename: Jian-Yuan
authors.initials: JY
authors.lastname: Huang
authors.affiliation: Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: O'Keeffe Ahern
authors.affiliation: Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.
authors.forename: Lara
authors.initials: L
authors.lastname: Cutlar
authors.affiliation: Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.
authors.forename: Dezhong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University , Taipei, Taiwan , 100, R.O.C.
authors.forename: Feng-Huei
authors.initials: FH
authors.lastname: Lin
authors.affiliation: School of Materials Science and Engineering, Tianjin University , Tianjin, 300072, P.R.C.|Charles Institute of Dermatology, School of Medicine, University College Dublin , Dublin 4, Ireland.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Wang
mesh_terms: D002470:Cell Survival / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000235:genetics*; D004952:Esters / Q000737:chemistry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics; D006801:Humans; D011108:Polymers / Q000737:chemistry / Q000627:therapeutic use; D014162:Transfection
chemical_list: D004952:Esters; D011108:Polymers; D004247:DNA