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In vivo genome editing via the HITI method as a tool for gene therapy

In vivo genome editing via the HITI method as a tool for gene therapy

Using genome-editing technologies to correct specific mutations represents a potentially transformative new approach for treating genetic disorders. Despite rapid advances in the field of genome editing, it is still unclear whether the long-standing goal of in vivo targeted transgene integration is feasible. This is primarily because

Using genome-editing technologies to correct specific mutations represents a potentially transformative new approach for treating genetic disorders. Despite rapid advances in the field of genome editing, it is still unclear whether the long-standing goal of in vivo targeted transgene integration is feasible. This is primarily because current tools are inefficient. In particular, current technologies are incapable of targeted gene knock-in in non-dividing cells, the major building blocks of adult tissues. This poses a significant barrier for developing therapeutic strategies to treat a broad range of devastating genetic disorders. Recently, our group has developed a unique CRISPR/Cas9-based strategy, termed homology-independent targeted insertion (HITI), which enables targeted gene insertion in non-dividing cells, both in vitro and in vivo. This review will summarize current progress in developing this technology, and discuss the potential impact of HITI-based gene-correction therapies.



Li J, Zhang B, Ren Y, Gu S, Xiang Y, Du J. Intron targeting-mediated and endogenous gene integrity-maintaining knockin in zebrafish using the CRISPR/Cas9 system. Cell Res. 2015;25:634-7.



Suzuki K, Tsunekawa Y, Hernandez-Benitez R, Wu J, Zhu J, Kim EJ, et al. In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature. 2016;540:144-9.



Yao X, Wang X, Liu J, Hu X, Shi L, Shen X, et al. CRISPR/Cas9 - mediated precise targeted integration in vivo using a double cut donor with short homology arms. EBioMedicine. 2017;20:19-26.



Yao X, Wang X, Hu X, Liu Z, Liu J, Zhou H, et al. Homology-mediated end joining-based targeted integration using CRISPR/Cas9. Cell Res. 2017;27:801-14.



Luo J, Baranov P, Patel S, Ouyang H, Quach J, Wu F, et al. Human retinal progenitor cell transplantation preserves vision. J Biol Chem. 2014;289:6362-71.

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November 13, 2017

In vivo genome editing via the HITI method as a tool for gene therapy

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