In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration

Keiichiro Suzuki, Yuji Tsunekawa, Reyna Hernández-Benítez, Jun Wu, Jie Zhu, Euiseok J. Kim, Fumiyuki Hatanaka, Mako Yamamoto, Toshikazu Araoka, Zhe Li, Masakazu Kurita, Tomoaki Hishida, Mo Li, Emi Aizawa, Shicheng Guo, Song Chen, April Goebl, Rupa Devi Soligalla, Jing Qu, Tingshuai JiangXin Fu, Maryam Jafari, Concepcion Rodriguez Esteban, W. Travis Berggren, Jeronimo Lajara, Estrella Nuñez-Delicado, Pedro Guillen, Josep M. Campistol, Fumio Matsuzaki, Guang-Hui Liu, Pierre J. Magistretti, Kun Zhang, Edward M. Callaway, Kang Zhang, Juan Carlos Izpisua Belmonte

Research output: Contribution to journalArticlepeer-review

740 Scopus citations


Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient1, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders2. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)3, 4 technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.
Original languageEnglish (US)
Pages (from-to)144-149
Number of pages6
Issue number7631
StatePublished - Nov 16 2016


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