φc31 integrase induces chromosomal aberrations in primary human fibroblasts

被引：64

作者：

Liu, J. ^{[1
]}

Jeppesen, I. ^{[1
]}

Nielsen, K. ^{[1
]}

Jensen, T. G. ^{[1
]}

机构：

[1] John F Kennedy Inst, Natl Eye Clin, DK-2600 Glostrup, Denmark

来源：

GENE THERAPY | 2006年 / 13卷 / 15期

关键词：

nonviral gene transfer; site-specific integration; chromosomal instability;

D O I：

10.1038/sj.gt.3302789

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：

phi c31 integrase is investigated as a novel tool for nonviral gene therapy as the enzyme can direct site-specific integration into a host chromosome. In order to investigate effects of phi c31 integrase expression in normal human cells, we have generated stably transfected primary human fibroblasts expressing the enzyme. All control cells were cytogenetically normal, but in cells expressing fc31 integrase, numerous chromosomal abnormalities including various translocations were found, suggesting that the enzyme itself acts as a mutagen.

引用

页码：1188 / 1190

页数：3

共 15 条

[11] Site-specific genomic integration produces therapeutic Factor IX levels in mice [J].

Olivares, EC ;

Hollis, RP ;

Chalberg, TW ;

Meuse, L ;

Kay, MA ;

Calos, MP .

NATURE BIOTECHNOLOGY, 2002, 20 (11) :1124-1128

[12] Stable nonviral genetic correction of inherited human skin disease [J].

Ortiz-Urda, S ;

Thyagarajan, B ;

Keene, DR ;

Lin, Q ;

Fang, M ;

Calos, MP ;

Khavari, PA .

NATURE MEDICINE, 2002, 8 (10) :1166-1170

[13] φC31 integrase-mediated nonviral genetic correction of junctional epidermolysis bullosa [J].

Ortiz-Urda, S ;

Thyagarajan, B ;

Keene, DR ;

Lin, Q ;

Calos, MP ;

Khavari, PA .

HUMAN GENE THERAPY, 2003, 14 (09) :923-928

[14] In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family [J].

Thorpe, HM ;

Smith, MCM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5505-5510

[15] Site-specific genomic integration in mammalian cells mediated by phage φC31 integrase [J].

Thyagarajan, B ;

Olivares, EC ;

Hollis, RP ;

Ginsburg, DS ;

Calos, MP .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (12) :3926-3934

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