2022
DOI: 10.1016/j.stemcr.2021.11.011
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An episomal DNA vector platform for the persistent genetic modification of pluripotent stem cells and their differentiated progeny

Abstract: The genetic modification of stem cells (SCs) is typically achieved using integrating vectors, whose potential integrative genotoxicity and propensity for epigenetic silencing during differentiation limit their application. The genetic modification of cells should provide sustainable levels of transgene expression, without compromising the viability of a cell or its progeny. We developed nonviral, nonintegrating, and autonomously replicating minimally sized DNA nanovectors to persistently genetically modify SCs… Show more

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Cited by 16 publications
(24 citation statements)
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References 68 publications
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“…Miniplasmids, lacking any bacterial sequences, are less likely to be silenced, but also lack replication competence and are diluted out in actively dividing cell populations. This limitation has been overcome by the production of pSMAR vectors, which contain scaffold/matrix attachment regions (SMARs) that allow them to be replicated and maintained throughout many mitotic cell divisions in both mouse and human stem cells and throughout differentiations ( Mulia et al, 2021 ; Roig-Merino et al, 2022 ). Interestingly, while stable during mitotic division, pSMAR vectors are lost upon meiotic divisions and cannot be propagated through the germ line.…”
Section: Delivery Of Inducible Genetic Elementsmentioning
confidence: 99%
“…Miniplasmids, lacking any bacterial sequences, are less likely to be silenced, but also lack replication competence and are diluted out in actively dividing cell populations. This limitation has been overcome by the production of pSMAR vectors, which contain scaffold/matrix attachment regions (SMARs) that allow them to be replicated and maintained throughout many mitotic cell divisions in both mouse and human stem cells and throughout differentiations ( Mulia et al, 2021 ; Roig-Merino et al, 2022 ). Interestingly, while stable during mitotic division, pSMAR vectors are lost upon meiotic divisions and cannot be propagated through the germ line.…”
Section: Delivery Of Inducible Genetic Elementsmentioning
confidence: 99%
“…Among the non-viral gene delivery systems described thus far, the scaffold/matrix attachment regions (SMARs) are non-integrating vectors suitable for PSC engineering and can autonomously replicate without causing molecular or genetic damage. Moreover, SMARs provide sustained transgene expression during the reprogramming and differentiation of PSC and their progenies ( 111 ).…”
Section: A Safety Switch For a Safer Cell Therapymentioning
confidence: 99%
“…In contrast to the CMV promoter, the CAG promoter is less prone to cytosine methylation [ 71 ]. It has been successfully used for the generation of induced pluripotent stem cells (iPSCs) [ 72 ] and the genetic engineering of stem cells [ 73 ].…”
Section: Transgene Expressionmentioning
confidence: 99%
“…Recently, the group of Harbottle fundamentally modified S/MAR-based episomes, developing a new generation of S/MAR vectors termed nano-S/MARs (nS/MAR) [ 73 , 75 ]. The prokaryotic vector backbone was depleted for CpG sites, and inserting an RNA OUT element [ 121 , 123 ] enabled antibiotic-free selection.…”
Section: Mitotic Stabilitymentioning
confidence: 99%
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