Image-guided, Intravascular Hydrodynamic Gene Delivery to Skeletal Muscle in Pigs

被引：34

作者：

Kamimura, Kenya ^{[1
]}

Zhang, Guisheng ^{[1
]}

Liu, Dexi ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA

来源：

MOLECULAR THERAPY | 2010年 / 18卷 / 01期

关键词：

NAKED PLASMID DNA; EXPRESSION IN-VIVO; TRANSGENE EXPRESSION; EFFICIENT EXPRESSION; THERAPY VECTORS; LIVER; INJECTION; OPTIMIZATION; DYSTROPHIN; ELEMENTS;

D O I：

10.1038/mt.2009.206

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Development of an effective, safe, and convenient method for gene delivery to muscle is a critical step toward gene therapy for muscle-associated diseases. Toward this end, we have explored the possibility of combining the image-guided catheter insertion technique with the principle of hydrodynamic delivery to achieve muscle-specific gene transfer in pigs. We demonstrate that gene transfer efficiency of the procedure is directly related to flow rate, injection pressure, and injection volume. The optimal gene delivery was achieved at a flow rate of 15 ml/second with injection pressure of 300 psi and injection volume equal to 1.5% of body weight. Under such a condition, hydrodynamic injection of saline containing pCMV-Luc (100 mu g/ml) resulted in luciferase activity of 10(6) to 10(7) relative light units (RLU)/mg of proteins extracted from the targeted muscle 5 days after hydrodynamic gene delivery. Result from immunohistochemical analysis revealed 70-90% transfection efficiency of muscle groups in the hindlimb and persistent reporter gene expression for 2 months in transfected cells. With an exception of transient edema and elevation of creatine phosphokinase, no permanent tissue damage was observed. These results suggest that the image-guided, intravenous hydrodynamic delivery is an effective and safe method for gene delivery to skeletal muscle.

引用

页码：93 / 100

页数：8

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