Multigene human artificial chromosome vector delivery with herpes simplex virus 1 amplicons

Chan, David Yiu Leung; Moralli, Daniela; Wheatley, Lucy; Jankowska, Julia; Monaco, Zoia Larin

doi:10.1016/j.yexcr.2020.111840

Cited by 6 publications

(5 citation statements)

References 9 publications

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“…Given that the maximum capacity of HSV-1-based vectors is 152 kbp, and that the centromeric region length is approximately 42 kbp, a target transgene of up to 110 kbp in length can be inserted into the considered HAC. An important indication that the HSV-1 replicon-based HAC may be used in cell therapy in the future was its successful transfer to human ESCs [ 72 ] and iPSCs [ 73 ].…”

Section: Main Hac Types and Methods For Their Productionmentioning

confidence: 99%

“…Recently, the method for assembling this HAC has been improved. Human cells were transduced with two different vectors, one of which contained the alpha satellite sequence of human chromosome 17, and the other contained target genes [ 73 ]. When these vector constructs met in the cell nucleus, they recombined with each other to form a stable HAC with double the size of the initial one (Fig.…”

Section: Main Hac Types and Methods For Their Productionmentioning

confidence: 99%

“…Учитывая, что максимальная емкость векторов на основе HSV-1 составляет 152 т.п.н., а длина центромерного участка равна приблизительно 42 т.п.н., в рассматриваемую ИХЧ можно встраивать целевой трансген длиной до 110 т.п.н. Важным указанием на то, что ИХЧ, сконструированная на основе репликона HSV-1, может быть в перспективе использована в клеточной терапии, стал ее успешный перенос в ЭСК [72] и ИПСК [73] человека.…”

Section: ихч на основе ампликона Hsv-1unclassified

“…Недавно был усовершенствован метод сборки ИХЧ рассматриваемого типа. Клетки человека трансдуцировали двумя различными векторами, один из которых содержал альфа-сателлитную последовательность хромосомы 17 человека, а другой -целевые гены [73]. После попадания таких векторных конструкций в ядро клетки между ними происходила рекомбинация, образовывалась стабильная ИХЧ, размер которой был в 2 раза больше первоначальной (рис.…”

Section: ихч на основе ампликона Hsv-1unclassified

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Human Artificial Chromosomes and Their Transfer to Target Cells

2022

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Human artificial chromosomes (HACs) have been developed as genetic vectors with the capacity to carry large transgenic constructs or entire gene loci. HACs represent either truncated native chromosomes or de novo synthesized genetic constructs. The important features of HACs are their ultra-high capacity and ability to self-maintain as independent genetic elements, without integrating into host chromosomes. In this review, we discuss the development and construction methods, structural and functional features, as well as the areas of application of the main HAC types. Also, we address one of the most technically challenging and time-consuming steps in this technology the transfer of HACs from donor to recipient cells.

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Section: Main Hac Types and Methods For Their Productionmentioning

confidence: 99%

Section: Main Hac Types and Methods For Their Productionmentioning

confidence: 99%

Section: ихч на основе ампликона Hsv-1unclassified

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Human Artificial Chromosomes and Their Transfer to Target Cells

2022

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“…As such, different delivery strategies were explored, utilising either the fusion machinery of viruses [ 54 ] or virus-based amplicons [ 55 ]. While the development and improvement of HACs experienced significant progress within the last decade [ 56 , 57 , 58 , 59 ], their design and construction require particular considerations and utilities that differ from those needed for nonviral vectors. As these have been comprehensively reviewed elsewhere [ 60 , 61 , 62 ], we will focus in this review on the three nonviral vector systems EBV-based replicons, Sleeping Beauty, and S/MAR-based episomes.…”

Section: Introductionmentioning

confidence: 99%

Episomes and Transposases—Utilities to Maintain Transgene Expression from Nonviral Vectors

Kreppel

Hagedorn

2022

Genes

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The efficient delivery and stable transgene expression are critical for applications in gene therapy. While carefully selected and engineered viral vectors allowed for remarkable clinical successes, they still bear significant safety risks. Thus, nonviral vectors are a sound alternative and avoid genotoxicity and adverse immunological reactions. Nonviral vector systems have been extensively studied and refined during the last decades. Emerging knowledge of the epigenetic regulation of replication and spatial chromatin organisation, as well as new technologies, such as Crispr/Cas, were employed to enhance the performance of different nonviral vector systems. Thus, nonviral vectors are in focus and hold some promising perspectives for future applications in gene therapy. This review addresses three prominent nonviral vector systems: the Sleeping Beauty transposase, S/MAR-based episomes, and viral plasmid replicon-based EBV vectors. Exemplarily, we review different utilities, modifications, and new concepts that were pursued to overcome limitations regarding stable transgene expression and mitotic stability. New insights into the nuclear localisation of nonviral vector molecules and the potential consequences thereof are highlighted. Finally, we discuss the remaining limitations and provide an outlook on possible future developments in nonviral vector technology

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