PMID- 23023424 OWN - NLM STAT- MEDLINE DCOM- 20140228 LR - 20190724 IS - 1347-5231 (Electronic) IS - 0031-6903 (Linking) VI - 132 IP - 9 DP - 2012 TI - [Development of target-specific gene therapy system by controlling distribution of interferon]. PG - 1057-61 AB - Interferon-gamma (IFN-gamma) is a type II IFN that possesses various biological activities including antivirus effect and antitumor effect. Because of its potent biological activities, IFN-gamma has been used as a therapeutic treatment for cancer patients and is expected to be a therapeutic for other diseases. As the half-life of IFN-gamma in blood circulation is very short, IFN-gamma gene therapy, in which IFN-gamma gene is used to continuously supply IFN-gamma protein, is a promising approach because it can continuously supply IFN-gamma. To improve therapeutic effect of IFN-gamma-based gene therapy, it is important to control the spatiotemporal distribution of IFN-gamma expressed from the plasmid DNA vector encoding IFN-gamma. We developed a method to regulate the time profile of IFN-gamma expressed from plasmid DNA by modifying vector backbone. In addition, we developed a method that can increase retention time of IFN-gamma in blood circulation by designing IFN-gamma encoded in plasmid vector as a fusion protein with mouse serum albumin (MSA). Regulation of time profile of IFN-gamma expression was highly effective in avoiding unwanted effect of IFN-gamma without decreasing therapeutic effect. In addition, gene delivery of MSA-IFN-gamma fusion protein increased retention time of IFN-gamma in blood circulation than native IFN-gamma gene delivery did. Thus, designing both plasmid vector and therapeutic protein encoded by the vector is a promising approach to controlling the spatiotemporal distribution of proteins which can increase the therapeutic potency of IFN-gamma-based gene therapy as well as safety of in vivo IFN-gamma gene therapy. FAU - Takahashi, Yuki AU - Takahashi Y AD - Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. ytakahashi@pharm.kyoto-u.ac.jp LA - jpn PT - English Abstract PT - Journal Article PT - Review PL - Japan TA - Yakugaku Zasshi JT - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JID - 0413613 RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Genetic Therapy/*methods MH - Genetic Vectors MH - Humans MH - Interferon-gamma/*genetics MH - Mice EDAT- 2012/10/02 06:00 MHDA- 2014/03/01 06:00 CRDT- 2012/10/02 06:00 PHST- 2012/10/02 06:00 [entrez] PHST- 2012/10/02 06:00 [pubmed] PHST- 2014/03/01 06:00 [medline] AID - DN/JST.JSTAGE/yakushi/132.1057 [pii] AID - 10.1248/yakushi.132.1057 [doi] PST - ppublish SO - Yakugaku Zasshi. 2012;132(9):1057-61. doi: 10.1248/yakushi.132.1057.