W8L2 Gene drive Flashcards
How does mouse t haplotype work
-in the t-haplotype contain antidote and toxin.
-the toxin are able to diffuse to other cell causing WT spree to die
-furthermore, found o chromosome 17, inverted region so suppressed recombination
Homing endonucleases
-enzyme that induce double stranded DNA breaks at specific, long (and rare) target sequences in the genome
Cas9
DsDNA break induced by Cas9 is directed by a 20 base guide RNA(gRNA) that matches the target sequences
Laboratory gene drive demonstration
-Targeting a female fertility gene results in bias toward male offspring that carry the gene drive
-initial pop of 300 equal sex ratio. Population crash start at the eight generation
Zebra fish split gene drive for optimizing gene drive design
-Aromatase enzyme converts testosterone to estrogen
-cyp19a1a -/- cause female to male sex reversal
-as bio security precaution, essential elements of the gene drive are split into unlinked part of the genome
Inserting gene drive into non-model species
-for European carp and cane toad: direct injection of CRISPR reagent into egg
-for mammals: nuclear transfer of CIRSPER edited cell
Problem of spatial heterogeneity
-gene drive chasing the Wildtype alleles
The problem with generation time
-different animal have different generation time, the longer the generation time is, the longer gene drive fixation process will be (time to eradicate )
Solution to the risk of introducing gene drive to a non target population
-simple to engineer a gene drive resistant allele compare to the gene drive itself
-this resistance can cause the gene drive allel to extinction
Risk of gene drive resistance
-resistance can be induced, de novo or preexisting in the population
-solution: incorporate multiple gRNA modules into the gene drive
example of gene editing wildlife
-American chestnut tree with transgene for chestnut blight resistance- (not approved)
-northern quolls with small gene edit for resistance to cane toad toxin- inprogress
-frog with transgene for skin secreted neutralizing antibody against chytrid funguses-in progress
-thylacine de-extinction in progress