Nanoparticulate Nonviral Agent for the Effective Delivery of pDNA and siRNA to Differentiated Cells and Primary Human T Lymphocytes

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...

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Bibliographic Details
Published in:Biomacromolecules 2012-11, Vol.13 (11), p.3463-3474
Main Authors: Schallon, Anja, Synatschke, Christopher V, Jérôme, Valérie, Müller, Axel H. E, Freitag, Ruth
Format: Article
Language:English
Subjects:
Animals
Applied sciences
Biological and medical sciences
CD4 Antigens - analysis
CD4 Antigens - genetics
Cell Differentiation
Cells, Cultured
CHO Cells
Cricetinae
Exact sciences and technology
Gene Expression
Gene Transfer Techniques
General pharmacology
Genetic Vectors
HEK293 Cells
Humans
Inorganic and organomineral polymers
Jurkat Cells
Medical sciences
Mice
Nanoparticles
Nucleic Acids - chemistry
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Plasmids - genetics
Polymerization
Properties and characterization
RNA Interference
RNA, Small Interfering - genetics
T-Lymphocytes - cytology
Transfection
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Summary: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.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm3012055