GMO 2.0: Gene Drives

A CRISPR–Cas9 gene drive targeting doubles causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat. Biotechnol. (2018) Kyrou K, et al study found A CRISPR–Cas9 gene drive construct spread rapidly in caged mosquitoes, reaching 100% prevalence within 7–11 generations (population collapse)...We note that these proof-of-principle experiments cannot conclude that this drive is resistance proof.

Inter-homologue repair in fertilized human eggs? (2018) Nature: 560,E5–E7. Eli D., et al found that CRISPA/Cas9 has the potential to reduce disease-causing alleles, but inadvertent changes to the human germ line, including rearrangements, long deletions, and loss of heterozygosity,could have serious consequences that affect development, predisposition to cancer and fertility.

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements(2018). Nature Biotechnology. pp.1-7. Kosicki M., et al summarized “… we show that DNA breaks introduced by single-guide RNA/Cas9 frequently resolved into deletions extending over many kilobases. Furthermore, lesions distal to the cut site and crossover events were identified. The observed genomic damage in mitotically active cells caused by CRISPR–Cas9 editing may have pathogenic consequences.

Evolution of Resistance Against CRISPR/Cas9 Gene Drive. (2017) Genetics 205(2):827–841. Unkless, Clark and Messer (2017) showed that resistance to standard CRISPR/Cas9 gene drive (CGD) approaches should evolve almost inevitably in most natural populations... The key factor determining the probability that resistance evolves is the overall rate at which resistance alleles arise at the population level by mutation or nonhomologous end joining(NHEJ.

CRISPR/Cas9 systems targeting β-globin and CCR5 genes have substantial off-target activity. (2013) Nucleic Acids Research, 41 (20), 9584-9592. Cradick, Fine, Antico & Bao, found that the repair of the on-and off-target cleavage resulted in a wide variety of insertions, deletions and point mutations