The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives.
| Autor: | Verkuijl SAN; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom.; Department of Zoology, University of Oxford, Oxford, United Kingdom., Ang JXD; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom., Alphey L; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom., Bonsall MB; Department of Zoology, University of Oxford, Oxford, United Kingdom., Anderson MAE; Arthropod Genetics, The Pirbright Institute, Pirbright, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2022 Mar 28; Vol. 10, pp. 856981. Date of Electronic Publication: 2022 Mar 28 (Print Publication: 2022). |
| DOI: | 10.3389/fbioe.2022.856981 |
| Abstrakt: | Making discrete and precise genetic changes to wild populations has been proposed as a means of addressing some of the world's most pressing ecological and public health challenges caused by insect pests. Technologies that would allow this, such as synthetic gene drives, have been under development for many decades. Recently, a new generation of programmable nucleases has dramatically accelerated technological development. CRISPR-Cas9 has improved the efficiency of genetic engineering and has been used as the principal effector nuclease in different gene drive inheritance biasing mechanisms. Of these nuclease-based gene drives, homing endonuclease gene drives have been the subject of the bulk of research efforts (particularly in insects), with many different iterations having been developed upon similar core designs. We chart the history of homing gene drive development, highlighting the emergence of challenges such as unintended repair outcomes, "leaky" expression, and parental deposition. We conclude by discussing the progress made in developing strategies to increase the efficiency of homing endonuclease gene drives and mitigate or prevent unintended outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Verkuijl, Ang, Alphey, Bonsall and Anderson.) |
| Databáze: | MEDLINE |
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