title: Biodegradable hybrid recombinant block copolymers for non-viral gene transfection.
abstract: Thermal targeting of therapeutic genes can enhance local gene concentration to maximize their efficacy. However, lack of safe and efficient carriers has impeded the development of this delivery option. Herein, we report the preparation and evaluation of a hybrid recombinant material, p[Asp(DET)](53)ELP(1-90), that possess a thermo-responsive elastin-like polypeptide (ELP) segment and a diethylenetriamine (DET) modified poly-L-aspartic acid segment. The term, hybrid, indicates that the material was prepared by genetic engineering and synthetic chemistry. In summary, the thermal phase transition behavior and cytotoxicity of the biodegradable copolymer were studied. The polyplexes formed by the copolymer and pGL4 plasmid were characterized by dynamic light scattering and ζ-potential measurements. The polyplexes retained the thermal phase transition behavior conferred by the copolymer; however, they exhibited a two-step transition process not seen with the copolymer. The polyplexes also showed appreciable transfection efficiency with low cytotoxicity.
authors: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
authors: Tze-Haw H
authors: TH
authors: Chen
authors: Younsoo
authors: Y
authors: Bae
authors: Darin Y
authors: DY
authors: Furgeson
authors: Glen S
authors: GS
authors: Kwon
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D019556:COS Cells; D002522:Chlorocebus aethiops; D004549:Elastin / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D044367:Phase Transition; D010957:Plasmids / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D011506:Proteins / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry; D012212:Rheology; D013696:Temperature; D014162:Transfection / Q000379:methods*
chemical_list: D011073:Polyamines; D011506:Proteins; C573822:p(Asp(DET))53ELP(1-90); C005391:diethylenetriamine; D001224:Aspartic Acid; D004549:Elastin