title: Nanoparticulate nonviral agent for the effective delivery of pDNA and siRNA to differentiated cells and primary human T lymphocytes.
abstract: Delivery of polynucleotides such as plasmid DNA (pDNA) and siRNA to nondividing and primary cells by nonviral vectors presents a considerable challenge. In this contribution, we introduce a novel type of PDMAEMA-based star-shaped nanoparticles that (i) are efficient transfection agents in clinically relevant and difficult-to-transfect human cells (Jurkat T cells, primary T lymphocytes) and (ii) can efficiently deliver siRNA to human primary T lymphocytes resulting to more than 40% silencing of the targeted gene. Transfection efficiencies achieved by the new vectors in serum-free medium are generally high and only slightly reduced in the presence of serum, while cytotoxicity and cell membrane disruptive potential at physiological pH are low. Therefore, these novel agents are expected to be promising carriers for nonviral gene transfer. Moreover, we propose a general design principle for the construction of polycationic nanoparticles capable of delivering nucleic acids to the above-mentioned cells.
authors.affiliation: Process Biotechnology, University of Bayreuth, 95440 Bayreuth, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schallon
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Synatschke
authors.forename: Valérie
authors.initials: V
authors.lastname: Jérôme
authors.forename: Axel H E
authors.initials: AH
authors.lastname: Müller
authors.forename: Ruth
authors.initials: R
authors.lastname: Freitag
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D016466:CHO Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D006224:Cricetinae; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D053758:Nanoparticles; D009696:Nucleic Acids / Q000737:chemistry; D010957:Plasmids / Q000235:genetics*; D058105:Polymerization; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology*; D014162:Transfection
chemical_list: D015704:CD4 Antigens; D009696:Nucleic Acids; D034741:RNA, Small Interfering