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

Abstract

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.

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Acknowledgements

We are grateful to Y. Xia and D. O’Keefe for help with manuscript preparation. KS was supported by JSPS KAKENHI (15K21762). JCIB was supported by The Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002), The G. Harold and Leila Y. Mathers Charitable Foundation, NIH (R01HL123755), The McKnight Foundation, The Moxie Foundation, Fundacion Dr. Pedro Guillen, and Universidad Católica San Antonio de Murcia (UCAM).

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Correspondence to Keiichiro Suzuki.

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Suzuki, K., Izpisua Belmonte, J.C. In vivo genome editing via the HITI method as a tool for gene therapy. J Hum Genet 63, 157–164 (2018). https://doi.org/10.1038/s10038-017-0352-4

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