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

Yamada, Hidetoshi; Li, Yanze C.; Nishikawa, Mitsuo; Oshimura, Mitsuo; Inoue, Toshiaki

doi:10.1007/s10038-008-0268-0

Cited by 15 publications

(9 citation statements)

References 26 publications

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“…A comprehensive list of genes loaded on HAC vectors is available in the recent review by Kazuki and Oshimura [22]. Among them, the following genes that are represented as genomic copies that include all regulatory elements: human beta-globin [46], CFTR [52, 53], Factor IX [54], STAT3 [55], TP53 [56], DYS [57], VHL , and NBS1 [58]. However, in almost all cases, the copy number of the gene in the HAC was not precisely controlled either because of the presence of multiple gene accepter sites in the HAC or because the gene was inserted into the HAC during its de novo formation, i.e.…”

Section: Hacs For Correction Of Gene-deficiencies In Recipient Human mentioning

confidence: 99%

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

Kouprina¹,

Earnshaw

Masumoto

et al. 2012

Cell. Mol. Life Sci.

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Since their description in the late 1990s, human artificial chromosomes (HACs) carrying a functional kinetochore were considered as a promising system for gene delivery and expression with a potential to overcome many problems caused by the use of viral-based gene transfer systems. Indeed, HACs avoid the limited cloning capacity, lack of copy number control and insertional mutagenesis due to integration into host chromosomes that plague viral vectors. Nevertheless, until recently, HACs have not been widely recognized because of uncertainties of their structure and the absence of a unique gene acceptor site. The situation changed a few years ago after engineering of HACs with a single loxP gene adopter site and a defined structure. In this review, we summarize recent progress made in HAC technology and concentrate on details of two of the most advanced HACs, 21HAC generated by truncation of human chromosome 21 and alphoidtetO-HAC generated de novo using a synthetic tetO-alphoid DNA array. Multiple potential applications of the HAC vectors are discussed, specifically the unique features of two of the most advanced HAC cloning systems.

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Section: Hacs For Correction Of Gene-deficiencies In Recipient Human mentioning

confidence: 99%

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

Kouprina¹,

Earnshaw

Masumoto

et al. 2012

Cell. Mol. Life Sci.

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“…Established HACs are readily propagated in many different vertebrate cell types Yamada et al 2008;Cardinale et al 2009;Iida et al 2010), indicating that the mechanisms maintaining centromere identity and promoting kinetochore assembly are conserved across species. Indeed, in one study, the alphoidtetO HAC was transferred by microcell-mediated fusion from human HT1080 cells to chicken DT40 cells, to Chinese Hamster CHO cells and back to HT1080 cells whilst being retrofitted with various markers and recombination sites (Iida et al 2010).…”

Section: Breaking the Hac Formation Barriermentioning

confidence: 99%

“…In addition to providing valuable vectors for the cloning of large DNA sequences and their promises for gene delivery and therapy (Burke et al 1987;Basu and Willard 2005;Tsuduki et al 2006;Yamada et al 2008), both of which are not dealt with in this review, human artificial chromosomes (HACs) mimic endogenous chromosomes in kinetochore structure and mitotic behaviour (Nakashima et al 2005) and are amenable to controlled manipulation without affecting endogenous chromosomes and overall cell viability.…”

Section: Introductionmentioning

confidence: 99%

HACking the centromere chromatin code: insights from human artificial chromosomes

et al. 2012

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The centromere is a specialized chromosomal region that serves as the assembly site of the kinetochore. At the centromere, CENP-A nucleosomes form part of a chromatin landscape termed centrochromatin. This chromatin environment conveys epigenetic marks regulating kinetochore formation. Recent work sheds light on the intricate relationship between centrochromatin state, the CENP-A assembly pathway and the maintenance of centromere function. Here, we review the emerging picture of how chromatin affects mammalian kinetochore formation. We place particular emphasis on data obtained from Human Artificial Chromosome (HAC) biology and the targeted engineering of centrochromatin using synthetic HACs. We discuss implications of these findings, which indicate that a delicate balance of histone modifications and chromatin state dictates both de novo centromere formation and the maintenance of centromere identity in dividing cell populations.

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“…HACs/MACs generally harbor loxP sites for gene loading. In system (b), circular vectors such as plasmids, P1 artificial chromosomes (PACs), and bacterial artificial chromosomes (BACs) were successfully loaded onto HACs/MACs by the Cre/loxP system for various purposes including functional analysis, monitoring system development, and gene therapy [58][59][60][61][62][63][64] (Fig. 3b).…”

Section: Gene-loading Techniques For Hacs/macsmentioning

confidence: 99%

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

et al. 2017

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

Cited by 15 publications

References 26 publications

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

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

HACking the centromere chromatin code: insights from human artificial chromosomes

Combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models

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