Repeat mediated excision of gene drive elements for restoring wild-type populations.

Here, we demonstrate that single strand annealing (SSA) can be co-opted for the precise autocatalytic excision of a drive element. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE). By engineering direct repeats flanking the drive allele and inducing a double-strand DNA break (DSB) at a second endonuclease target site within the allele, we increased the utilization of SSA repair.

Repeat mediated excision of gene drive elements for restoring wild-type populations.

We demonstrate here that single strand annealing (SSA) repair can be co-opted for the precise autocatalytic excision of a drive element. Although SSA is not the predominant form of DNA repair in eukaryotic organisms, we increased the likelihood of its use by engineering direct repeats at sites flanking the drive allele, and then introducing a double-strand DNA break (DSB) at a second endonuclease target site encoded within the drive allele. We have termed this technology Repeat Mediated Excision of a Drive Element (ReMEDE).

Expansions to the MGDrivE suite for simulating the efficacy of novel gene-drive constructs in the control of mosquito-borne diseases.

Objective: The MGDrivE (MGDrivE 1 and MGDrivE 2) modeling framework provides a flexible and expansive environment for testing the efficacy of novel gene-drive constructs for the control of mosquito-borne diseases. However, the existing model framework did not previously support several features necessary to simulate some types of intervention strategies. Namely, current MGDrivE versions do not permit modeling of small molecule inducible systems for controlling gene expression in gene drive designs or the inheritance patterns of self-eliminating gene drive mechanisms.

Genetic Approaches for Controlling CRISPR-based Autonomous Homing Gene Drives.

CRISPR-based autonomous homing gene drives are a potentially transformative technology with the power to reduce the prevalence of, or even eliminate, vector-borne diseases, agricultural pests, and invasive species. However, there are a number of regulatory, ethical, environmental, and sociopolitical concerns surrounding the potential use of gene drives, particularly regarding the possibility for any unintended outcomes that might result from such a powerful technology. Therefore, there is an imminent need for countermeasures or technologies capable of exerting precise spatiotemporal control of gene drives, if their transformative potential is ever to be fully realized.