Sequence-specific modification of genomic DNA by small DNA fragments
Dieter C. Gruenert, … , Federica Sangiuolo, Kaarin K. Goncz
Dieter C. Gruenert, … , Federica Sangiuolo, Kaarin K. Goncz
Published September 1, 2003
Citation Information: J Clin Invest. 2003;112(5):637-641. https://doi.org/10.1172/JCI19773.
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Sequence-specific modification of genomic DNA by small DNA fragments

Abstract

Small DNA fragments have been used to modify endogenous genomic DNA in both human and mouse cells. This strategy for sequence-specific modification or genomic editing, known as small-fragment homologous replacement (SFHR), has yet to be characterized in terms of its underlying mechanisms. Genotypic and phenotypic analyses following SFHR have shown specific modification of disease-causing genetic loci associated with cystic fibrosis, β-thalassemia, and Duchenne muscular dystrophy, suggesting that SFHR has potential as a therapeutic modality for the treatment of monogenic inherited disease.

Authors

Dieter C. Gruenert, Emanuela Bruscia, Giuseppe Novelli, Alessia Colosimo, Bruno Dallapiccola, Federica Sangiuolo, Kaarin K. Goncz

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Figure 1

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Schematic representation of different SDF configurations possible in SFH...
Schematic representation of different SDF configurations possible in SFHR-mediated modification of a target sequence. The SDF can interact with the target sequence as (a) sense and/or (b) antisense ssDNA, or as (c) dsDNA. The ssDNA can be introduced either as individual strands (sense and antisense) or as denatured cDNA strands. The enzymatic mechanisms involved require further elucidation.