Persistence in muscle of an adenoviral vector that lacks all viral genes

被引:231
作者
Chen, HH
Mack, LM
Kelly, R
Ontell, M
Kochanek, S
Clemens, PR
机构
[1] UNIV PITTSBURGH,DEPT CELL BIOL & PHYSIOL,PITTSBURGH,PA 15213
[2] INST PASTEUR,DEPT MOL BIOL,F-75724 PARIS 15,FRANCE
[3] BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030
关键词
Duchenne muscular dystrophy; gene transfer; lacZ transgenic mice; vector persistence;
D O I
10.1073/pnas.94.5.1645
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Genetic correction of inherited muscle diseases, such as Duchenne muscular dystrophy, will require long term expression of the recombinant protein following gene transfer, We have shown previously that a new adenoviral vector that lacks all viral genes expressed both full-length dystrophin and beta-gatactosidase in mdr (dystrophin-deficient) mouse muscle. We observed a significant histologic improvement of vector-transduced mdx muscle before the eventual loss of vector-encoded transgene expression, In this study, we investigated whether an immunological response against vector-encoded beta-galactosidase contributed to the loss of vector expression and affected vector persistence in muscle. Intramuscular vector injection in control normal mice resulted in an early and complete loss of beta-galactosidase expression accompanied by predominantly CD4(+) and CD8(+) lymphocytic infiltration and a significant loss of vector DNA, In contrast, intramuscular vector injection in lacZ transgenic mice resulted in persistent expression of beta-galactosidase for at least 84 days with no evidence of inflammation or significant loss of vector DNA, Our studies demonstrate that, in the absence of an immune response induced by beta-galactosidase expression, an adenoviral vector lacking all viral genes is stably maintained in muscle.
引用
收藏
页码:1645 / 1650
页数:6
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