title: Evaluation of generations 2, 3 and 4 arginine modified PAMAM dendrimers for gene delivery.
abstract: It is a matter of concern to develop and design synthetic non-viral gene carriers with high transfection efficiency and low cytotoxicity in gene therapy. Recently, various arginine conjugated dendrimers showed better performance in transfection and greater viability than polyethyleneimine (PEI). In this study, we synthesized and investigated e-PAM-R G2, 3 and 4 which are biodegradable polyamidoamine (PAMAM) dendrimers modified with arginine and compared that with PAMAM-R series containing amide bonds for gene carriers. For plasmid DNA delivery, the transfection efficiency of e-PAM-R G4 was higher than G3 and G2 and similar to PAMAM-R G4 with favorable cell viability. Moreover, they indicated significantly higher suppression of TEL/AML1 protein, maybe due to rapid olidonucleotide (ODNs) release through biodegradability of e-PAM-R. These results suggest that biodegradable and non-toxic e-PAM-R may be useful carriers for the gene including plasmid DNA, antisense ODNs and si-RNA.
authors: School of Chemistry & Molecular Engineering, Seoul National University, Seoul, Republic of Korea.
authors: Hye Yeong
authors: HY
authors: Nam
authors: Hwa Jeong
authors: HJ
authors: Hahn
authors: Kihoon
authors: K
authors: Nam
authors: Woo-Hyung
authors: WH
authors: Choi
authors: Yunseong
authors: Y
authors: Jeong
authors: Dong-Eun
authors: DE
authors: Kim
authors: Jong-Sang
authors: JS
authors: Park
mesh_terms: D021581:Active Transport, Cell Nucleus; D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D019677:Artificial Gene Fusion; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism; D050091:Dendrimers; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011073:Polyamines / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D001120:Arginine; D050676:Core Binding Factor Alpha 2 Subunit; D004247:DNA; D021881:DNA, Catalytic; D050091:Dendrimers; D016376:Oligonucleotides, Antisense; D011073:Polyamines; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C104700:PAMAM Starburst; C493728:RUNX1 protein, human