Exogenous Gene Expression and Growth Regulation of Hematopoietic Cells Via a Novel Human Artificial Chromosome

Overview

Journal J Hum Genet

Specialty Genetics

Date 2005 Dec 8

PMID 16333524

Citations 6

Authors

Hidetoshi Yamada

Atsushi Kunisato

Masahiro Kawahara

Candice G T Tahimic

Xianying Ren

Hiroshi Ueda

Teruyuki Nagamune

Motonobu Katoh

Toshiaki Inoue

Mitsuo Nishikawa

Mitsuo Oshimura

Affiliations

Soon will be listed here.

Abstract

A number of gene delivery systems are currently being developed for potential use in gene therapy. Here, we demonstrate the feasibility of 21deltaqHAC, a newly developed human artificial chromosome (HAC), as a gene delivery system. We first introduced a 21deltaqHAC carrying an EGFP reporter gene and a geneticin-resistant gene (EGFP-21deltaqHAC) into hematopoietic cells by microcell-mediated chromosome transfer. These HAC-containing hematopoietic cells showed resistance to geneticin, expressed EGFP and retained the ability to differentiate into various lineages, and the EGFP-21deltaqHAC was successfully transduced into primary hematopoietic cells. Hematopoietic cells harboring the EGFP-21deltaqHAC could still be detected at two weeks post-transplantation in immunodeficient mice. We also showed effective expansion of hematopoietic cells by introducing the 21deltaqHAC containing ScFvg, a gp130-based chimeric receptor that transmits growth signals in response to specific-antigen of this receptor. All of these results demonstrate the usefulness of HAC in gene therapy.

Citing Articles

A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.

Oshimura M, Uno N, Kazuki Y, Katoh M, Inoue T Chromosome Res. 2015; 23(1):111-33.

PMID: 25657031 PMC: 4365188. DOI: 10.1007/s10577-014-9459-z.

De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications.

Katona R Chromosome Res. 2015; 23(1):143-57.

PMID: 25596828 DOI: 10.1007/s10577-014-9458-0.

A new generation of human artificial chromosomes for functional genomics and gene therapy.

Kouprina N, Earnshaw W, Masumoto H, Larionov V Cell Mol Life Sci. 2012; 70(7):1135-48.

PMID: 22907415 PMC: 3522797. DOI: 10.1007/s00018-012-1113-3.

Human artificial chromosomes for gene delivery and the development of animal models.

Kazuki Y, Oshimura M Mol Ther. 2011; 19(9):1591-601.

PMID: 21750534 PMC: 3182354. DOI: 10.1038/mt.2011.136.

Introduction of a CD40L genomic fragment via a human artificial chromosome vector permits cell-type-specific gene expression and induces immunoglobulin secretion.

Yamada H, Li Y, Nishikawa M, Oshimura M, Inoue T J Hum Genet. 2008; 53(5):447-453.

PMID: 18322642 DOI: 10.1007/s10038-008-0268-0.

References

Saffery R, Choo K . Strategies for engineering human chromosomes with therapeutic potential. J Gene Med. 2002; 4(1):5-13. DOI: 10.1002/jgm.236. View

Larin Z, Mejia J . Advances in human artificial chromosome technology. Trends Genet. 2002; 18(6):313-9. DOI: 10.1016/S0168-9525(02)02679-3. View

Doherty A, Fisher E . Microcell-mediated chromosome transfer (MMCT): small cells with huge potential. Mamm Genome. 2003; 14(9):583-92. DOI: 10.1007/s00335-003-4002-0. View

Ueda T, Tsuji K, Yoshino H, Ebihara Y, Yagasaki H, Hisakawa H . Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptor. J Clin Invest. 2000; 105(7):1013-21. PMC: 377479. DOI: 10.1172/JCI8583. View

Kawahara M, Kimura H, Ueda H, Nagamune T . Selection of genetically modified cell population using hapten-specific antibody/receptor chimera. Biochem Biophys Res Commun. 2004; 315(1):132-8. DOI: 10.1016/j.bbrc.2004.01.030. View

Ren X, Katoh M, Hoshiya H, Kurimasa A, Inoue T, Ayabe F . A novel human artificial chromosome vector provides effective cell lineage-specific transgene expression in human mesenchymal stem cells. Stem Cells. 2005; 23(10):1608-16. DOI: 10.1634/stemcells.2005-0021. View

Kakeda M, Hiratsuka M, Nagata K, Kuroiwa Y, Kakitani M, Katoh M . Human artificial chromosome (HAC) vector provides long-term therapeutic transgene expression in normal human primary fibroblasts. Gene Ther. 2005; 12(10):852-6. DOI: 10.1038/sj.gt.3302483. View

Grimes B, Warburton P, Farr C . Chromosome engineering: prospects for gene therapy. Gene Ther. 2002; 9(11):713-8. DOI: 10.1038/sj.gt.3301763. View

Kimura T, Wang J, Minamiguchi H, Fujiki H, Harada S, Okuda K . Signal through gp130 activated by soluble interleukin (IL)-6 receptor (R) and IL-6 or IL-6R/IL-6 fusion protein enhances ex vivo expansion of human peripheral blood-derived hematopoietic progenitors. Stem Cells. 2000; 18(6):444-52. DOI: 10.1634/stemcells.18-6-444. View

10.

Kuroiwa Y, Tomizuka K, Shinohara T, Kazuki Y, Yoshida H, Ohguma A . Manipulation of human minichromosomes to carry greater than megabase-sized chromosome inserts. Nat Biotechnol. 2000; 18(10):1086-90. DOI: 10.1038/80287. View

11.

Katoh M, Ayabe F, Norikane S, Okada T, Masumoto H, Horike S . Construction of a novel human artificial chromosome vector for gene delivery. Biochem Biophys Res Commun. 2004; 321(2):280-90. DOI: 10.1016/j.bbrc.2004.06.145. View