Human Genetics

, Volume 138, Issue 1, pp 1–19 | Cite as

Ways of improving precise knock-in by genome-editing technologies

  • Svetlana A. SmirnikhinaEmail author
  • Arina A. Anuchina
  • Alexander V. Lavrov


Despite the recent discover of genome-editing methods, today we can say these approaches have firmly entered our life. Two approaches—knocking out malfunctioning gene allele or correcting the mutation with precise knock-in—can be used in hereditary monogenic diseases treatment. The latter approach is relatively ineffective. Modern data about the ways of repair of double-strand DNA breaks formed by nucleases are presented in this review. The main part of the review is devoted to the ways of increasing precise and effective knock-in: inhibition of non-homologous end joining and stimulation of homology-directed repair key factors, use of small molecules with unknown mechanism of action, cell-cycle synchronization and cell-cycle-dependent activity of Cas9, donor molecule design, selection, alternative methods for insertion and other approaches.



The section “Knock-in enhancement” was supported by the grant of the Russian Science Foundation (Agreement 17-75-20095), and the sections “DNA repair pathways” was supported by the Russian Academy of Sciences (Program “Fundamental researches for biomedical technologies”) and the state assignment of FASO Russia.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of MutagenesisFederal State Budgetary Institution “Research Centre for Medical Genetics”MoscowRussia
  2. 2.Department of Molecular and Cellular GeneticsThe Russian National Research Medical University Named after N.I. PirogovMoscowRussia

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