The authors of MS #JEB-2020-00222 provide a broad and timely review of the diverse gene drive systems (including the evolution of resistance) and use that information to discuss strategies for their application to control pests and diseases using synthetic drivers. After a short general overview, the authors describe all major driver systems in turn, including relevant examples. In their synthesis of promising applications, they draw much attention to the avoidance (or minimization) of resistance, which I consider integral to the design of any synthetic driver.

I found the review to be well-written, thorough and appealing in scope to the readership of JEB, but I suggest a few minor changes for clarification that I would like the authors to consider:

25 This opening statement is unclear. Do you mean that organisms are controlled by genes? There is clearly more to an organism than genes, let alone ‘cooperating’ genes, and “created” itself may have some non-evolutionary connotations here.
Then also, I do not think “succeed” is the best word here for an allele (it might simply increase in frequency). In my view, it is not even needed as “spread through populations” basically says it all already.

32 Is this order of organisms chosen based on prevalence? Otherwise I would find it more logical to group insects with the other animal taxa here (e.g. between nematodes and mice).

34 It should be made clearer what “This” is referring to - e.g. the drive itself or the fact that it damages male function? (for now I rule out the example or the endosymbiont...)

36 Since a seed is a plant embryo, i.e. after gamete fusion, how does this exclude any ‘paternal’ contributions? Would eggs, egg cells or ovules be more appropriate?

218 imposes -> impose. Then also, please provide the scientific name of maize at first mention.

265-276 This section on genetic incompatibility focuses on male killing and feminization, but cytoplasmic incompatibility can also result in varying levels of general progeny lethality (i.e. both sexes), e.g. see Wolbachia in Drosophila, Tribolium or Culex, or Cardinium in some Hympenoptera. There is substantial literature on these systems. And then there are other endosymbionts with a diversity of effects (beyond the ones mentioned here) across arthropods (e.g. see Goodacre & Martin, 2012, Insects 3:246-261).

383 Diasemopsis meigenii should be italicized

406 gamete-killing

620 trade off

Fig. 1 I would suggest generating a bit more contrast between “Driver” in the center and the background for better visibility on a grayscale (e.g. darker font or larger yellow center).