2007
DOI: 10.1016/j.jmb.2007.04.079
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Engineered I-CreI Derivatives Cleaving Sequences from the Human XPC Gene can Induce Highly Efficient Gene Correction in Mammalian Cells

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Cited by 131 publications
(112 citation statements)
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“…The previously described I-CreI engineered derivatives are heterodimers. Therefore, they are obtained by coexpression of 2 different monomers in the target cell (10,30,33), resulting in the formation of 3 molecular species (the heterodimer and 2 homodimers). Studies with heterodimeric Zinc Finger Nucleases (34,35) showed that such homodimeric byproducts can be cytotoxic.…”
Section: Discussionmentioning
confidence: 99%
“…The previously described I-CreI engineered derivatives are heterodimers. Therefore, they are obtained by coexpression of 2 different monomers in the target cell (10,30,33), resulting in the formation of 3 molecular species (the heterodimer and 2 homodimers). Studies with heterodimeric Zinc Finger Nucleases (34,35) showed that such homodimeric byproducts can be cytotoxic.…”
Section: Discussionmentioning
confidence: 99%
“…Site-specific meganucleases have challenging design criteria owing to the single-chained recognition and cleavage domains, although successful modification has been described for a number of applications [15–17]. In the context of gene therapy, meganucleases have for example been modeled for targeted recombination and correction of the RAG1 gene associated with severe combined immunodeficiency (SCID) [18] in hematopoietic stem cells (HSCs) and the XPC gene associated with Xeroderma Pigmentosum in skin cells [19]. Applications within T cell therapies include prevention of graft-versus-host disease (GvHD) via meganuclease-mediated TCR α-chain knockout under conditions for optimal T cell stimulation and meganuclease cleavage efficiency [15].…”
Section: Toolsmentioning
confidence: 99%
“…33 Finally, two engineered MGNs cleaving two different human genes, XPC and RAG1, have been described in the literature. 21,[33][34][35] These recent developments provide the potential to target any chromosomal locus with engineered MGNs. Thus, these proteins represent a universal tool to mutate the genome at specific sequence target and are thus very promising for precise and efficient genome modifications.…”
Section: Introductionmentioning
confidence: 99%