Bi-HAC Vector System toward Gene and Cell Therapy

Iida, Yuichi; Kazuki, Yasuhiro; Hayashi, Masahiro; Ueda, Yasuji; Hasegawa, Mamoru; Kouprina, Natalay; Larionov, Vladimir; Oshimura, Mitsuo

doi:10.1021/sb400166j

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…In contrast, all top-down HACs are linear, precisely engineered, and stably maintained in host cells. The bi-HAC system utilizing both top-down and bottom-up HACs, and benefitting from the advantages of both, was reported previously [50].…”

Section: Characteristics Of Hacs/macsmentioning

confidence: 94%

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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Section: Characteristics Of Hacs/macsmentioning

confidence: 94%

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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“…Numerous other HACs have been developed since these first studies (Mills et al 1999;Mejia and Larin 2000;Grimes et al 2001;Kouprina et al 2003;Kazuki et al 2011;Mandegar et al 2011;Iida et al 2014;Takiguchi et al 2014). They have been constructed by either a "topdown" approach, by which the first mitotically stable minichromosomes were formed by chromosome truncation with telomeric sequences (Brown et al 1994;Farr et al 1995;Heller et al 1996;Mills et al 1999;Kazuki et al 2011); or a "bottom-up" approach ( Figure 2), in which naked DNA is introduced into cells either by transfection (Henning et al 1999;Ikeno et al 2002;Kouprina et al 2003;Suzuki et al 2006) or by transduction with herpex simplex virus 1 (Moralli et al 2006;Mandegar et al 2011), thus generating de novo artificial chomosomes.…”

Section: Human Artificial Chromosomes Development: a Historic Viewmentioning

confidence: 99%

Using human artificial chromosomes to study centromere assembly and function

et al. 2017

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Abstract:Centromeres are the site of assembly of the kinetochore, which directs chromosome segregation during cell division. Active centromeres are characterized by the presence of nucleosomes containing CENP-A and a specific chromatin environment that resembles that of active genes. Recent work using Human Artificial Chromosomes (HAC) sheds light on the fine balance of different histone post-translational modifications and transcription that exists at centromeres for kinetochore assembly and maintenance. Here, we review the use of HAC technology to understand centromere assembly and function. We put particular emphasis on studies using the alphoidtetO HAC, whose centromere can be specifically modified for epigenetic engineering studies. Author Comments:We suggest Professor Erich Nigg as an Editor (not found in the "Request Editor" list), who invited us to write this review.Response to Reviewers: Comments for the Author:Reviewer #1: Since there has been significant progress over the last few years with regards to HAC technology, particularly with alphoidtetO HACs, a review on this topic would be welcomed in the field, especially by these authors, who are world experts on Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationthis topic. The review is mostly satisfying, but I would suggest two areas where the authors would be well served to make additions/changes to avoid disappointing readers hoping for more focus/organization/clarity. First, since the goal of this review is to "review the use of HAC technology to understand centromere assembly and function", it would be especially helpful if the authors summarized the evolution of HAC technology and the findings that came from targeting different tetR fusion proteins to the alphoidtetO HACs (probably most effectively in a table or schematic).We thank the reviewer for the thoughtful review of our MS. Following the reviewer´s advice, a table has been added explaining the findings that came from the alphoidtetO HAC studies in a timeline manner (Table 1).Second, more discussion on the pitfalls of current HACs would be desirable (currently only a couple sentences is mentioned in the future directions). From how it is written they sound so great that a reader would probably wonder why they are not used more widely in the research lab and/or clinic. There are problems with them, and it would be more clear and interesting, in my opinion, if more of the problems were laid out/challenges addressed.A description of limitations of the HAC technology have been added in the text, first limitations for HAC clinical use (p. 8-9) and additional limitations that should be overcome in the final remarks (p. 23). Some other changes that I'd suggest:1. It's confusing to refer to the same DNA as "alpha satellite", "α-satellite", and "alpha-satellite" throughout the review (most notably in the first two lines of the second paragraph). Why not just refer to it as "α-satellite" DNA?We changed the term to α-satellite DNA throughout the text to maintain consist...

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“…Most recently, the HAC could be used for functional study of BRCA-1 tumor suppressor gene (Kononenko et al 2014 ). Furthermore, two different HAC, a stable 21HAC and a removable tet-O HAC provides a unique bi-HAC vector system for transient gene expression (Iida et al 2014 ).…”

Section: Expression Of Genes In Hac/macmentioning

confidence: 99%

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

et al. 2015

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Microcell-mediated chromosome transfer (MMCT) is a technique to transfer a chromosome from defined donor cells into recipient cells and to manipulate chromosomes as gene delivery vectors and open a new avenue in somatic cell genetics. However, it is difficult to uncover the function of a single specific gene via the transfer of an entire chromosome or fragment, because each chromosome or fragment contains a set of numerous genes. Thus, alternative tools are human artificial chromosome (HAC) and mouse artificial chromosome (MAC) vectors, which can carry a gene or genes of interest. HACs/MACs have been generated mainly by either a “top-down approach” (engineered creation) or a “bottom-up approach” (de novo creation). HACs/MACs with one or more acceptor sites exhibit several characteristics required by an ideal gene delivery vector, including stable episomal maintenance and the capacity to carry large genomic loci plus their regulatory elements, thus allowing the physiological regulation of the introduced gene in a manner similar to that of native chromosomes. The MMCT technique is also applied for manipulating HACs and MACs in donor cells and delivering them to recipient cells. This review describes the lessons learned and prospects identified from studies on the construction of HACs and MACs, and their ability to drive exogenous gene expression in cultured cells and transgenic animals via MMCT. New avenues for a variety of applications to bio-medical challenges are also proposed.

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Bi-HAC Vector System toward Gene and Cell Therapy

Cited by 7 publications

References 38 publications

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

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

Using human artificial chromosomes to study centromere assembly and function

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

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