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

[1]

[Anonymous], CHROMOSOME ABNORMALI

[2] Site-specific cassette exchange and germline transmission with mouse ES cells expressing φC31 integrase [J].

Belteki, G ;

Gertsenstein, M ;

Ow, DW ;

Nagy, A .

NATURE BIOTECHNOLOGY, 2003, 21 (03) :321-324

[3] Integration specificity of phage φC31 integrase in the human genome [J].

Chalberg, TW ;

Portlock, JL ;

Olivares, EC ;

Thyagarajan, B ;

Kirby, PJ ;

Hillman, RT ;

Hoelters, J ;

Calos, MP .

JOURNAL OF MOLECULAR BIOLOGY, 2006, 357 (01) :28-48

[4] A direct comparison of two nonviral gene therapy vectors for somatic integration:: In vivo evaluation of the bacteriophage integrase φc31 and the Sleeping Beauty transposase [J].

Ehrhardt, A ;

Xu, H ;

Huang, Z ;

Engler, JA ;

Kay, MA .

MOLECULAR THERAPY, 2005, 11 (05) :695-706

[5] Site-Specific Integration with φC31 Integrase for Prolonged Expression of Therapeutic Genes [J].

Ginsburg, Daniel S. ;

Calos, Michele P. .

NON-VIRAL VECTORS FOR GENE THERAPY, SECOND EDITION: PART 2, 2005, 54 :179-187

[6] Construction of transgenic Drosophila by using the site-specific integrase from phage φC31 [J].

Groth, AC ;

Fish, M ;

Nusse, R ;

Calos, MP .

GENETICS, 2004, 166 (04) :1775-1782

[7] In vivo correction of murine hereditary tyrosinemia type I by φC31 integrase-mediated gene delivery [J].

Held, PK ;

Olivares, EC ;

Aguilar, CP ;

Finegold, M ;

Calos, MP ;

Grompe, M .

MOLECULAR THERAPY, 2005, 11 (03) :399-408

[8] Phage integrases for the construction and manipulation of transgenic mammals [J].

Roger P Hollis ;

Stephanie M Stoll ;

Christopher R Sclimenti ;

Jennifer Lin ;

Yanru Chen-Tsai ;

Michele P Calos .

Reproductive Biology and Endocrinology, 1 (1)

[9] Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells [J].

Loonstra, A ;

Vooijs, M ;

Beverloo, HB ;

Al Allak, B ;

van Drunen, E ;

Kanaar, R ;

Berns, A ;

Jonkers, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :9209-9214

[10]

Mitelman F, 1995, ISCN INT SYSTEM HUMA

← 1 2 →