Non-viral Nanoparticles Research Articles

779. Oral Delivery of Non-Viral DNA Nanoparticles for Hemophilia A

Hemophilia A is a defect in coagulation factor VIII, which is predominantly produced in liver and secreted into plasma at a level of 100-200 ng/ml. Hemophilia A is an attractive model for non-viral gene delivery since levels as low as 1-2% FVIII can affect bleeding. In addition, FVIII can be processed from non-liver cell types. While non-viral gene delivery has advantages of production and safety compared to viral gene therapy, the transient nature of gene expression makes re-administration necessary, therefore an oral route of administration highly desirable. We previously reported preliminary results in hemophilia A mice orally administered chitosan-FVIII DNA nanoparticles, including phenotypic bleeding correction in 4/5 mice given the highest DNA dose. Levels of functional FVIII by chromogenic assay were modest. However a thrombin assay revealed significantly greater thrombin generation in mice given chitosan-DNA nanoparticles as compared to naked DNA.

Advances in cystic fibrosis gene therapy

The first cystic fibrosis gene therapy trials were carried out in 1993, and although proof-of-principle for gene transfer to the lungs was established, efficiency was generally low. The authors review the most recent advances in preclinical airway gene transfer and summarize the results from the latest clinical trials. Recent clinical trials report encouraging results. Repeat administration of adeno-associated virus to the lung was safe. Nonviral nanoparticles used, for the first time, in the nose of cystic fibrosis patients were also safe and led to partial correction of the chloride transport defect in nasal epithelium. Important advances have been made in preclinical research, including the development of new viral and nonviral gene transfer agents and improved plasmid DNA. In addition, physical delivery methods, such a magnetofection and electroporation, are being assessed to improve nonviral gene transfer. Considerable progress has been made in understanding and overcoming the problems associated with gene transfer to airway epithelial cells, the target cells for cystic fibrosis gene therapy. It has also been recognized that novel preclinical and clinical assays are crucial for the success of cystic fibrosis gene therapy, and considerable effort is currently being put into assay development and trial designs.

A novel nonviral nanoparticle gene vector: Poly-L-lysine-silica nanoparticles

DNA delivery is a core technology for gene structure and function research as well as clinical settings. The ability to safely and efficiently targeted transfer foreign DNA into cells is a fundamental goal in biotechnology. With the development of nanobiotechnology, nanoparticle gene vectors brought about new hope to reach the goal. In our research, silica nanoparticles (SiNP) were synthesized first in a microemulsion system polyoxyethylene nonylphenyl ether (OP-10)/cyclohexane/ammonium hydroxide, at the same time the effects of SiNP size and its distribution were elucidated by orthogonal analysis; then poly-L-lysine (PLL) was linked on the surface of SiNP by nanoparticle surface energy and electrostatically binding; lastly a novel complex nanomateial—poly-L-lysine-silica nanoparticles (PLL-SiNP) was prepared. The analysis of plasmid DNA binding and DNase I enzymatic degradation discovered that PLL-SiNP could bind DNA, and protect it against enzymatic degradation. Cell transfection showed that PLL-SiNP could efficiently transfer PEGFPC-2 plasmid DNA into HNE1 cell line. These results indicated that PLL-SiNP was a novel nonviral nanoparticle gene vector, and would probably play an important role in gene structure and function research as well as gene therapy.