Development of an ultrasound-responsive and mannose-modified gene carrier for DNA vaccine therapy.
Development of a gene delivery system to transfer the gene of interest selectively and efficiently into targeted cells is essential for achievement of sufficient therapeutic effects by gene therapy. Here, we succeeded in developing the gene transfection method using ultrasound (US)-responsive and mannose-modified gene carriers, named Man-PEG(2000) bubble lipoplexes. Compared with the conventional lipofection method using mannose-modified carriers, this transfection method using Man-PEG(2000) bubble lipoplexes and US exposure enabled approximately 500-800-fold higher gene expressions in the antigen presenting cells (APCs) selectively in vivo. This enhanced gene expression was contributed by the improvement of delivering efficiency of nucleic acids to the targeted organs, and by the increase of introducing efficiency of nucleic acids into the cytoplasm followed by US exposure. Moreover, high anti-tumor effects were demonstrated by applying this method to DNA vaccine therapy using ovalbumin (OVA)-expressing plasmid DNA (pDNA). This US-responsive and cell-specific gene delivery system can be widely applied to medical treatments such as vaccine therapy and anti-inflammation therapy, which its targeted cells are APCs, and our findings may help in establishing innovative methods for in-vivo gene delivery to overcome the poor introducing efficiency of carriers into cytoplasm which the major obstacle associated with gene delivery by non-viral carriers.
Un
Keita
K
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kawakami
Shigeru
S
Suzuki
Ryo
R
Maruyama
Kazuo
K
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005805:Genes, MHC Class I; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008358:Mannose / Q000737:chemistry*; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D008081:Liposomes; D019444:Vaccines, DNA; D011092:Polyethylene Glycols; D008358:Mannose