Non-immunostimulatory nonviral vectors

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Feng LiuLeaf Huang

Abstract

The vectors for gene delivery are usually classified as viral and nonviral vectors. While the viral vectors are very efficient in transducing cells, safety concerns regarding their use in humans make nonviral vectors an attractive alternative. Among the nonviral vectors, the lipoplexes (complexes of cationic liposome/pDNA) are the most studied and represent the most promising approaches for human clinical trials. However, an inflammatory response is invariably associated with administration of the lipoplexes, which must be avoided in the clinical application. Here, we have successfully developed a nonimmunostimulatory vector for gene therapy. The vector possesses dual functions of: 1) efficiently delivering a gene to target cells and 2) codelivering DNA and inflammatory suppressors into the immune cells where the released suppressor can inhibit cytokine production. The inflammatory suppressors successfully delivered by the vector included glucocorticoids, a nonsteroidal anti-inflammatory drug (NSAID), an NF-kappaB inhibitor, and a natural compound from an herbal medicine. Intravenous injection of the vector dramatically suppressed the cytokine production induced by CpG motif pDNA, including TNF-alpha, IL-12 and IFN-gamma. This ...Continue Reading

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Citations

Sep 29, 2011·Applied Biochemistry and Biotechnology·Alicia Fernandez-FernandezAnthony J McGoron
Sep 10, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marc T AbramsLaura Sepp-Lorenzino
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