Robust and prolonged gene expression from injectable polymeric implants

被引:42
作者
Eliaz, RE [1 ]
Szoka, FC [1 ]
机构
[1] Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci & Pharmaceut Chem, San Francisco, CA 94143 USA
关键词
biomaterials; gene therapy/delivery; glycofurol; injectable implants; medical device; plasmid DNA; tissue engineering;
D O I
10.1038/sj.gt.3301786
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We introduce an injectable system for the formation of a biodegradable DNA-containing implant that releases DNA over a 2-month period to provide a robust and prolonged gene expression at the site. Sustained delivery of the appropriate plasmid DNA resulted in sustained expression of luciferase, the persistent appearance of secreted alkaline phosphatase in the serum and small blood vessel formation in the vicinity of the implant from the delivery of the development endothelial locus-1 gene. Local expression of development endothelial locus-1 protein promotes the development of blood vessels to meet the metabolic demands of new tissue and is a paradigm for the delivery of other growth factors that act locally to aid tissue regeneration. This delivery system involves simple preparation procedures and can be injected directly into the site, hence should be a useful approach to plasmid-based gene transfer for vaccination and tissue engineering.
引用
收藏
页码:1230 / 1237
页数:8
相关论文
共 26 条
[1]   Cationic lipids are essential for gene delivery mediated by intravenous administration of lipoplexes [J].
Barron, LG ;
Uyechi, LS ;
Szoka, FC .
GENE THERAPY, 1999, 6 (06) :1179-1183
[2]   Tissue engineering via local gene delivery [J].
Bonadio, J .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2000, 78 (06) :303-311
[3]   Localized, direct plasmid gene delivery in vivo:: prolonged therapy results in reproducible tissue regeneration [J].
Bonadio, J ;
Smiley, E ;
Patil, P ;
Goldstein, S .
NATURE MEDICINE, 1999, 5 (07) :753-759
[4]  
Chasin Mark, 1995, P1
[5]   Fluorometric determination of deoxyribonuclease I activity with PicoGreen [J].
Choi, SJ ;
Szoka, FC .
ANALYTICAL BIOCHEMISTRY, 2000, 281 (01) :95-97
[6]   Sustained release of cisplatin in dogs from an injectable implant delivery system [J].
Dunn, RL ;
Yewey, GL ;
Fujita, SM ;
Josephs, KR ;
Whitman, SL ;
Southard, GL ;
Dernell, WS ;
Straw, RC ;
Withrow, SJ ;
Powers, BE .
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS, 1996, 11 (04) :286-300
[7]  
Eliaz RE, 2000, J BIOMED MATER RES, V50, P388, DOI 10.1002/(SICI)1097-4636(20000605)50:3<388::AID-JBM13>3.3.CO
[8]  
2-6
[9]   Delivery of soluble tumor necrosis factor receptor from in-situ forming PLGA implants:: In-vivo [J].
Eliaz, RE ;
Wallach, D ;
Kost, J .
PHARMACEUTICAL RESEARCH, 2000, 17 (12) :1546-1550
[10]  
Harris LD, 1998, J BIOMED MATER RES, V42, P396, DOI 10.1002/(SICI)1097-4636(19981205)42:3<396::AID-JBM7>3.3.CO