Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin-inducible plasmid DNA.
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.
Namgung
Ran
R
Department of Chemistry, Pohang University of Science and Technology, Pohang, 790-784, Korea.
Brumbach
Jonathan H
JH
Jeong
Ji Hoon
JH
Yockman
James W
JW
Kim
Sung Wan
SW
Lin
Chao
C
Zhong
Zhiyuan
Z
Feijen
Jan
J
Engbersen
Johan F J
JF
Kim
Won Jong
WJ
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011073:Polyamines / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; C531249:Poly(amidoamine); D011073:Polyamines; D000077022:Survivin; D008156:Luciferases