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I understand that at the molecular level a CRISPR mediated gene drive works by copying the altered gene (and the drive containing CAS enzyme, and guide RNA) into the other chromosome containing the wild type allele through homology directed repair...Lets consider a suppressive drive that is designed to be lethal when the altered gene is present in Both copies of the chromosome (for example maybe organism is likely to die of a heart attack before reaching reproductive maturity)..... In a lethal suppression drive as described above, Where is this copying and homology directed repair happening. In the somatic cells of one of the “parents”, or the germline cells of the parents during meosis/gametogenesis? What happens when a organism containing wild type allele mates with an organism containing the drive?

If the drive and altered gene is copied in the somatic cells of the organism that was inserted in, then wouldn't the organism perish before, being able to pass on the drive/altered gene (given how our suppression drive is designed being lethal if both copies of gene are present)? Or is this copying happening during when the offspring is a zygote (thus all off offsprings somatic cells), or the germline of the offspring? If the copying is occurring in the Zygote stage, all somatic cells of the offspring will contain two copies of the altered gene and will be Homozygous recessive for the altered deleterious gene. Then how will the offspring be able to mate and SPREAD the drive before perishing (or not being able to reproduce). How is it ensured that drive copying only occurs during gametogenesis and does not alter the somatic cells in either parent or offspring? Because it seems to me for the drive and the altered gene to spread it can only happen during meosis/gametogensis...

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    $\begingroup$ Have you read, for example, the Wikipedia article on gene drives, or review articles like this one or this one? $\endgroup$
    – MattDMo
    Jan 16, 2023 at 23:53
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    $\begingroup$ Yes I read the Wikipedia and review article Did not quite clarify where and when the homology directed repair/copying is occurring for a suppressive gene drive.., Let us consider a suppressive drive that is supposed to kill organism before reaching reproductive maturity. Is this occurring during gametogenesis of the organism that contains the drive? Because in suppressive gene drives having TWO copies of the deleterious gene kills the organism, but one copy is benign. So if HEG/copying is happening in the somatic cells wouldn't the organism just die before able to pass gene? $\endgroup$ Jan 17, 2023 at 3:44
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    $\begingroup$ Crossposted on Medical Sciences SE $\endgroup$ Jan 17, 2023 at 12:35
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    $\begingroup$ I have closed the copy on Medical Sciences as I believe it is a better fit here. $\endgroup$ Jan 17, 2023 at 14:29
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    $\begingroup$ @MattDMo I think an answer based on those sources would be excellent. $\endgroup$
    – Bryan Krause
    Jan 18, 2023 at 16:16

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