Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles

被引：133
作者：
Suk, Jung Soo
Suh, Junghae
Choy, Kokleong
Lai, Samuel K.
Fu, Jie
Hanes, Justin
机构：
[1] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA
来源：
BIOMATERIALS | 2006年 / 27卷 / 29期
关键词：
gene therapy; CNS diseases; polymers; polyethylenimine (PEI);
D O I：
10.1016/j.biomaterials.2006.05.013
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
A number of neurodegenerative disorders may potentially be treated by the delivery of therapeutic genes to neurons. Nonviral gene delivery systems, however, typically provide low transfection efficiency in post-mitotic differentiated neurons. To uncover mechanistic reasons for this observation, we compared gene transfer to undifferentiated and differentiated SH-SY5Y cells using polyethylenimine (PEI)/DNA nanocomplexes. Differentiated cells exhibited substantially lower uptake of gene vectors. To overcome this bottleneck, RGD or HIV-1 Tat peptides were attached to PEI/DNA nanocomplexes via poly(ethylene glycol) (PEG) spacer molecules. Both RGD and Tat improved the cellular uptake of gene vectors and enhanced gene transfection efficiency of primary neurons up to 14-fold. RGD functionalization resulted in a statistically significant increase in vector escape from endosomes, suggesting it may improve gene delivery by more than one mechanism. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5143 / 5150
页数：8
相关论文
共 62 条
[1]   A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: Polyethylenimine [J].
Abdallah, B ;
Hassan, A ;
Benoist, C ;
Goula, D ;
Behr, JP ;
Demeneix, BA .
HUMAN GENE THERAPY, 1996, 7 (16) :1947-1954
[2]   Cdh1/Hct1-APC is essential for the survival of postmitotic neurons [J].
Almeida, A ;
Bolaños, JP ;
Moreno, S .
JOURNAL OF NEUROSCIENCE, 2005, 25 (36) :8115-8121
[3]   Coming to grips with integrin binding to ligands [J].
Arnaout, MA ;
Goodman, SL ;
Xiong, JP .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (05) :641-651
[4]  
Behr JP, 1997, CHIMIA, V51, P34
[5]   Dopamine toxicity involves mitochondrial complex I inhibition: implications to dopamine-related neuropsychiatric disorders [J].
Ben-Shachar, D ;
Zuk, R ;
Gazawi, H ;
Ljubuncic, P .
BIOCHEMICAL PHARMACOLOGY, 2004, 67 (10) :1965-1974
[6]  
Berry M, 2001, CURR OPIN MOL THER, V3, P338
[7]   A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].
BOUSSIF, O ;
LEZOUALCH, F ;
ZANTA, MA ;
MERGNY, MD ;
SCHERMAN, D ;
DEMENEIX, B ;
BEHR, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301
[8]   RGD peptides induce apoptosis by direct caspase-3 activation [J].
Buckley, CD ;
Pilling, D ;
Henriquez, NV ;
Parsonage, G ;
Threlfall, K ;
Scheel-Toellner, D ;
Simmons, DL ;
Albar, AN ;
Lord, JM ;
Salmon, M .
NATURE, 1999, 397 (6719) :534-539
[9]   Gene therapy progress and prospects: Parkinson's disease [J].
Burton, EA ;
Glorioso, JC ;
Fink, DJ .
GENE THERAPY, 2003, 10 (20) :1721-1727
[10]   Protective effects of intracerebral adenoviral-mediated GDNF gene transfer in a rat model of Parkinson's disease [J].
Chen, XW ;
Liu, WG ;
Yang, GY ;
Liu, ZG ;
Smith, S ;
Calne, DB ;
Chen, SD .
PARKINSONISM & RELATED DISORDERS, 2003, 10 (01) :1-7
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