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Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus

Authors: Yohei Matsubara; Tomoki Chiba; Kenichi Kashimada; Tomohiro Morio; Shuji Takada; Shuki Mizutani; Hiroshi Asahara;

Transcription activator-like effector nuclease-mediated transduction of exogenous gene into IL2RG locus

Abstract

X-linked severe combined immunodeficiency (SCID-X1) caused by mutations in interleukin 2 receptor gamma (IL2RG) gene threatens the survival of affected boys during the first year of life unless hematopoietic stem cell transplantation is provided. Although viral vector-mediated gene therapy has been successfully performed in patients with no HLA-matched donors, leukemia caused by vector-mediated insertional mutagenesis has been reported in some individuals. Transcription activator-like effector nuclease (TALEN) is an artificial sequence-specific endonuclease that is expected to revolutionize the precise correction of disease-causing mutations and eliminate the risk of insertional mutagenesis. Here, we report TALEN-mediated genome editing of the IL2RG locus. We transfected TALENs along with a targeting vector into Jurkat cells, and we confirmed the precise introduction of the exogenous gene into the IL2RG locus. In addition, we found that the length of homology arm in the targeting vector influenced the efficiency of TALEN-mediated homologous recombination.

Keywords

Base Sequence, Genome, Human, Reverse Transcriptase Polymerase Chain Reaction, Genetic Vectors, Molecular Sequence Data, Endonucleases, Flow Cytometry, Real-Time Polymerase Chain Reaction, Article, Blotting, Southern, Jurkat Cells, Mutagenesis, Insertional, Sequence Homology, Nucleic Acid, Mutation, Humans, DNA Breaks, Double-Stranded, RNA Editing, RNA, Messenger, Homologous Recombination, Interleukin Receptor Common gamma Subunit

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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
18
Average
Average
Top 10%
Green
gold