Applications of Anti-CRISPR Proteins in Genome Editing and Biotechnology

Kraus, Carolyn; Sontheimer, Erik J.

doi:10.1016/j.jmb.2023.168120

Cited by 8 publications

(2 citation statements)

References 108 publications

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“…The latter is achieved through the use of the naturally occurring anti-CRISPR (Acr) proteins, products of the evolutionary arms race between bacterial adaptive immune systems and bacteriophages 23 . Acrs have been used in several heterologous eukaryotic systems for temporal and spatial post-translational control of CRISPR-mediated gene editing, offering great potential for improvement of therapeutic uses of CRISPR 24 , 25 . Other than mammalian cells in which the functionality and adaptability of Acrs has been extensively researched, Acrs have also been proved effective in CRISPR-Cas inhibition in higher organisms, such as plants 26 , mice 27 and zebrafish 28 .…”

Section: Introductionmentioning

confidence: 99%

Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages

D’Amato,

Taxiarchi,

Galardini

et al. 2024

Nat Commun

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CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting gene drive was able to suppress laboratory Anopheles mosquito populations in small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework suggest that systems able to modulate or revert the action of gene drives, could be part of post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive to inhibit gene drive spread in age-structured Anopheles gambiae population under complex feeding and behavioural conditions. A stochastic model predicts the experimentally-observed genotype dynamics in age-structured populations in medium-sized cages and highlights the necessity of large-sized cage trials. These experiments and experimental-modelling framework demonstrate the effectiveness of the anti-drive in different scenarios, providing further corroboration for its use in controlling the spread of gene drive in Anopheles.

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Section: Introductionmentioning

confidence: 99%

Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages

D’Amato,

Taxiarchi,

Galardini

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Studying Acrs not only provides fundamental insights into the evolutionary arms race between prokaryotes and their viruses but additionally illuminates the key mechanisms of Cas proteins. Furthermore, Acrs can be repurposed for controlling Cas protein activity in genome editing or other biotechnological applications ( 9 ). In this issue of PNAS, Sun et al have studied structures of Cas9 bound to Acr protein AcrIIC4 and thereby uncovered a novel mechanism of Cas9 inhibition: preventing complete R-loop formation ( 10 ).…”

mentioning

confidence: 99%