Written by: Ashley Koca

Genetic engineering’s tool of the century may have been one-upped by UC-San Diego scientists’ newly engineered allelic drive. This new technique utilizes a second guide RNA (gRNA) to preferentially slice an unwanted allele as well as the usual insertion of the gene drive element. Researchers tested two versions of this new drive, a “copy-cutting” type and a “copy-grafting” technique as well. The future of GMOs is bound to change with allelic drive, allowing for safer, more accurately modified life forms more readily produced. 

The issue with the current efficiency of CRISPR, is that it works with rather substantially sized sequences while many beneficial traits such as pest-resistance and crop yield are dictated by small allelic edits too specific for CRISPR-Cas9. This new allelic drive possesses two versions, copy-cutting —which first uses a gRNA and Cas9 protein to slice one allele and promptly after employs a repairing mechanism/HDR to replace the sliced allele with a favored non-cleavable version—and also copy-grafting, a mechanism that replicates a small patch of the favored genome containing the desired trait near the gRNA site that is associated with close-range range sequences that are un-cleavable. 

Utilizing this new technique, researchers implemented the Notch gene (represented as N+ and N− to show loss and gain of function) in Drosophila melanogaster and observed the inheritance of both versions. Tagging N+ with Ds-Red, gRNA copied this element into the near-Notch yellow locus while the N-  NAX mutation remained natural. This experiment resulted in the DsRed-marked element showing super mendelian inheritance, the NAX16 allele proving to have higher inheritance, and, oddly, retrieving none of the N- alleles although it being possible. Interestingly, additional benefits to this new drive were found serendipitously. Lethal mosaicism was found to be an effect of the drive, eliminating all non-homologous end joining mutants; meaning, that this extraneous function guarantees the possibility of survival to edited organisms exclusively—eliminating mistakes. Ultimately the powers of shadow drive were recovered. Shadow drive allows lasting, maternally-passed Cas9-gRNA act as a backup for one generation if isolated from gRNA or Cas9 material. 

Allelic drive could provide assistance in the inheritance of favorable alleles in the crop industry and go even further to coalesce several favorable traits after introducing allele-specific gRNA to target each trait within each cross. What’s more, allelic drive could revert alleles back to their wild type to reverse pesticide resistance. The applications of this newfound technology are vast and can most obviously assist in improving efforts to correct the pitfalls of the agricultural industry. With such a promising future, hopefully allelic drive will soon be found to better the conditions of much more. 

Guichard, A., Haque, T., Bobik, M., Xu, X. S., Klanseck, C., Kushwah, R. B., . . . Bier, E. (2019). Efficient allelic-drive in Drosophila. Nature Communications,10(1). doi:10.1038/s41467-019-09694-w