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

Autor:	Chennuri PR; Department of Entomology and AgriLife Research, Texas A&M University, College Station, TX 77843, USA., Zapletal J; Department of Industrial and Systems Engineering, Texas A&M University, College Station, TX 77843, USA., Monfardini RD; Department of Entomology and AgriLife Research, Texas A&M University, College Station, TX 77843, USA., Ndeffo-Mbah ML; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.; Department of Epidemiology and Biostatistics, Texas A&M University, College Station, TX 77843, USA., Adelman ZN; Department of Entomology and AgriLife Research, Texas A&M University, College Station, TX 77843, USA., Myles KM; Department of Entomology and AgriLife Research, Texas A&M University, College Station, TX 77843, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 23. Date of Electronic Publication: 2023 Nov 23.
DOI:	10.1101/2023.11.23.568397
Abstrakt:	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). Incorporation of ReMEDE into the previously described mutagenic chain reaction (MCR) gene drive, targeting the yellow gene of Drosophila melanogaster , replaced drive alleles with wild-type alleles demonstrating proof-of-principle. Although the ReMEDE system requires further research and development, the technology has a number of attractive features as a gene drive mitigation strategy, chief among these the potential to restore a wild-type population without releasing additional transgenic organisms or large-scale environmental engineering efforts. Competing Interests: Competing Interests KMM and ZNA are inventors on US provisional patent application PCT/US2021/041951, submitted by Texas A&M University, which covers vector constructs that are pre-programmed to self-eliminate or self-remove at a predetermined time, and methods of making the same. PRC, JZ, RDM, MLNM declare no competing interests.
Databáze:	MEDLINE
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