A chromatin insulator protects retrovirus vectors from chromosomal position effects

被引：191

作者：

Emery, DW ^{[1
]}

Yannaki, E ^{[1
]}

Tubb, J ^{[1
]}

Stamatoyannopoulos, G ^{[1
]}

机构：

[1] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 16期

关键词：

D O I：

10.1073/pnas.160159597

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：

Recombinant murine retroviruses are widely used as delivery vectors for gene therapy. However, once integrated into a chromosome, these vectors often suffer from profound position effects, with vector silencing observed in vitro and in vivo. To overcome this problem, we investigated whether the HS4 chromatin insulator from the chicken beta-globin locus central region could protect a retrovirus vector from position effects. When used to flank a reporter vector, this element significantly increased the fraction of transduced cells that expressed the provirus in cultures and in mice transplanted with transduced marrow. These results demonstrate that a chromatin insulator can improve the expression performance of a widely used class of gene therapy vectors by protecting these vectors from chromosomal position effects.

引用

页码：9150 / 9155

页数：6

共 35 条

[1] In vivo selection of retrovirally transduced hematopoietic stem cells [J].

Allay, JA ;

Persons, DA ;

Galipeau, J ;

Riberdy, JM ;

Ashmun, RA ;

Blakley, RL ;

Sorrentino, BP .

NATURE MEDICINE, 1998, 4 (10) :1136-1143

[2] Long-term expression of the gene encoding green fluorescent protein in murine hematopoietic cells using retroviral gene transfer [J].

Bagley, J ;

Aboody-Guterman, K ;

Breakefield, X ;

Iacomini, J .

TRANSPLANTATION, 1998, 65 (09) :1233-1240

[3] Stopped at the border: boundaries and insulators [J].

Bell, AC ;

Felsenfeld, G .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 1999, 9 (02) :191-198

[4] The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].

Bell, AC ;

West, AG ;

Felsenfeld, G .

CELL, 1999, 98 (03) :387-396

[5] COMBINATION OF INTERLEUKIN-3 AND INTERLEUKIN-6 PRESERVES STEM-CELL FUNCTION IN CULTURE AND ENHANCES RETROVIRUS-MEDIATED GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS [J].

BODINE, DM ;

KARLSSON, S ;

NIENHUIS, AW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :8897-8901

[6] DEVELOPMENT OF A HIGH-TITER RETROVIRUS PRODUCER CELL-LINE CAPABLE OF GENE-TRANSFER INTO RHESUS-MONKEY HEMATOPOIETIC STEM-CELLS [J].

BODINE, DM ;

MCDONAGH, KT ;

BRANDT, SJ ;

NEY, PA ;

AGRICOLA, B ;

BYRNE, E ;

NIENHUIS, AW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (10) :3738-3742

[7] Improved amphotropic retrovirus-mediated gene transfer into hematopoietic stem cells [J].

Bodine, DM ;

Dunbar, CE ;

Girard, LJ ;

Seidel, NE ;

Cline, AP ;

Donahue, RE ;

Orlic, D .

COOLEYS ANEMIA: SEVENTH SYMPOSIUM, 1998, 850 :139-150

[8] LACK OF EXPRESSION FROM A RETROVIRAL VECTOR AFTER TRANSDUCTION OF MURINE HEMATOPOIETIC STEM-CELLS IS ASSOCIATED WITH METHYLATION IN-VIVO [J].

CHALLITA, PM ;

KOHN, DB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (07) :2567-2571

[9] A GFP reporter system to assess gene transfer and expression in human hematopoietic progenitor cells [J].

Cheng, L ;

Du, C ;

Murray, D ;

Tong, X ;

Zhang, YA ;

Chen, BP ;

Hawley, RG .

GENE THERAPY, 1997, 4 (10) :1013-1022

[10] Characterization of the chicken beta-globin insulator [J].

Chung, JH ;

Bell, AC ;

Felsenfeld, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (02) :575-580

← 1 2 3 4 →