Peer-reviewed by 3 reviewers with median rating of 12/20. Review process was triple-blinded.
Round 1 (12/20)
Conceptual advance and Impact8
This is an important observation that should be made available to those employing CRISPR-based approaches to HIV latency reversal
Please state the statistical test for which the "*" refer. Please make clear what is significantly different from mock, versus vector plus/minus gRNA
Conceptual advance and Impact3.5
Crucial control is missing for this study. Authors need to add the control, or change the text to make sure that conclusions correspond with their data.
I believe the correct term for mutant Ca9 would be dead-cas9 or dCas9, which specifies that the mutation eliminates catalytic activity.
Results & Discussion
An important missing control is an empty DNA vector that does not carry Cas9 nor gRNA. From this results, we are not sure if it is the Cas9 alone that causes this induction, or transfection of any vector would do the same.
Again, that a Cas9 vector alone causes an increase in gene activation raises doubts. I suggest the authors include a control transfection with a plasmid that does not express Cas9.
The description of statistical tests is missing.
Conceptual advance and Impact7.5
I did find the paper difficult to read. Revising the text would be beneficial.
I find the first paragraph difficult to read. I would recommend the authors to revise the text to make it flow better.