Can a Population Targeted by a CRISPR-Based Homing Gene Drive Be Rescued? - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue G3 Année : 2020

Can a Population Targeted by a CRISPR-Based Homing Gene Drive Be Rescued?

Résumé

CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations. This technique is based on the release of individuals carrying an engineered piece of DNA that can be preferentially inherited by the progeny. The development of countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also indicates that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues.
Fichier principal
Vignette du fichier
2020-rode_G3.pdf (2.13 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02978494 , version 1 (28-10-2020)

Licence

Paternité

Identifiants

Citer

Nicolas O. Rode, Virginie Courtier-Orgogozo, Florence Débarre. Can a Population Targeted by a CRISPR-Based Homing Gene Drive Be Rescued?. G3, 2020, 10 (9), pp.3403-3415. ⟨10.1534/g3.120.401484⟩. ⟨hal-02978494⟩
118 Consultations
52 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More