Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin-inducible plasmid DNA |
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| Authors: | Ran Namgung Jonathan H Brumbach Ji Hoon Jeong James W Yockman Sung Wan Kim Chao Lin Zhiyuan Zhong Jan Feijen Johan F J Engbersen Won Jong Kim |
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| Institution: | (1) Department of Chemistry, Pohang University of Science and Technology, Pohang, 790-784, Korea;(2) Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, 20 S 2030 E RM 205 BPRB, Salt Lake City, UT 84112-5820, USA;(3) College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea;(4) Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology and Institute for Biomedical Technology (BMTI), University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands;(5) Biomedical Polymers Laboratory, and Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 215123 Suzhou, People’s Republic of China |
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| Abstract: | A bioreducible poly(amido amine) (SS-PAA) gene carrier, known as poly (amido-butanol) (pABOL), was used to transfect a variety
of cancer and non-cancer cell lines. To obtain cancer-specific transgene expression for therapeutic efficiency in cancer treatment,
we constructed survivin-inducible plasmid DNA expressing the soluble VEGF receptor, sFlt-1, downstream of the survivin promoter
(pSUR-sFlt-1). Cancer-specific expression of sFlt-1 was observed in the mouse renal carcinoma (RENCA) cell line. pABOL enhanced
the efficiency of gene delivery compared to traditional carriers used in the past. Thus, a dual bio-responsive gene delivery
system was developed by using bioreducible p(ABOL) for enhanced intracellular gene delivery and survivin-inducible gene expression
system (pSUR-sFlt-1 or pSUR-Luc reporter gene) that demonstrates increased gene expression in cancer that has advantages over
current gene delivery systems. |
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