title: HPMA-oligolysine copolymers for gene delivery: optimization of peptide length and polymer molecular weight.
abstract: Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K(5) and K(10) oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K(15). Four HPMA-oligolysine copolymers were identified that met the desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Russell N
authors.initials: RN
authors.lastname: Johnson
authors.forename: David S H
authors.initials: DS
authors.lastname: Chu
authors.forename: Julie
authors.initials: J
authors.lastname: Shi
authors.forename: Joan G
authors.initials: JG
authors.lastname: Schellinger
authors.forename: Peter M
authors.initials: PM
authors.lastname: Carlson
authors.forename: Suzie H
authors.initials: SH
authors.lastname: Pun
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004355:Drug Stability; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008027:Light; D015394:Molecular Structure; D008970:Molecular Weight; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011487:Protein Conformation; D012542:Scattering, Radiation
chemical_list: D004337:Drug Carriers; D009842:Oligopeptides; D011109:Polymethacrylic Acids; D011107:Polylysine; C011533:Duxon; D004247:DNA