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The authors successfully addressed all comments made by the reviewers and myself. It is ready for publication once all typos are fixed (there are a lot a words without spaces, or words not separated by spaces once a period is used to end a sentence).
[# PeerJ Staff Note - this decision was reviewed and approved by Vladimir Uversky, a PeerJ Section Editor covering this Section #]
Please check the annotated pdf and proceed with the revisions asked.
According to the reviews, please broaden the information presented in the review, but keep it focused on the title of the manuscript. Also check the manuscript for typos and grammar errors.
This review described in this manuscript has cross-disciplinary interest and falls within the journal's scope. The review summarized recent findings about molecular farming in plant expression systems. They also described the strengths and current findings of molecular farming in plant expression systems well.
Although several review papers describe molecular farming using plant expression systems, this review mainly deals with cosmetically relevant fused proteins and transdermal drug delivery and their advantages. So, based on the manuscript they constituted, I believe there is a different point of view and accessibility to various audiences.
They introduce the subject well by emphasizing the importance of molecular farming using a plant expression system. They also introduce the strategy of the transdermal drug delivery system. Their review is based on the current limitations of molecular farming, providing for audiences interested in molecular farming using plant expression systems.
The survey methodology is consistent with an unbiased view, and they cited the references adequately. The review is well-organized and easy to follow. It also attracts attention from various audiences.
The introduction is well organized, and the conclusions meet the goals set out in the introduction. However, they have a little bit missing in their conclusion. Please include the limitations of your review theme, especially in molecular farming using plant expression systems and limitations of drug delivery systems, in the OUTLOOK or elsewhere in the manuscript.
L80: Please clarify all the references and add the refs.
I found many typos and spacing issues between characters (For example, L79: suc- cessully) throughout the manuscript. Overall, the text could use careful editing to improve clarity and readability.
While the review is within the journal´s scope, it lacks of a comprehensive perspective view and does not cover multiple disciplines. I found this review too specific. In the introduction, the authors state a focus on molecular farming strategies, but they subsequently only address a limited number of fusion proteins. I suggest the author present a more comprehensive perspective before going into the specific field of fused protein, as this could provide a broad-ranging and interdisciplinary interest to the study.
In general, the manuscript is well-written but there are a few terms that need to be fixed. For instance, in line 52, the word “rigoulous”, should be replaced by “rigorous”.
In line 218, please evaluate the meaning of the term “abound” and make any necessary corrections.
Kindly evaluate lines 34, 35, and 36. The sentence appears mistaken, especially given that the review does not discuss further the different methodologies for plant transformation.
According to the methodology, the review was restricted to Arabidopsis as the expression system and to only some products like transdermal peptides and cytokine. This narrow scope resulted in a review that was overly particular and biased. Other aspects that are relevant to molecular farming strategies include the use of different plant species/plant tissues, and plant systems, that are useful for heterologous protein expression, the incorporation of other elements important for successful expression such as promoters, terminators, enhancers, other recombinant proteins that have been in the focus of the skincare field, like collagen and other strategies related to protein engineering to produce new forms of proteins for skincare (not only fused proteins), industrial application aspects, such as the use of TAGS for purification, increasing the expression yields, among others. If the interest of this review is specific, please justify it in the introduction and explain the motivation to focus on only some aspects.
Since the Boolean search was performed as stated in the manuscript, please provide the correct string or group of strings using the Boolean operators. Pubmed offers different options for searches. Please indicate if the words were searched in all the fields of the manuscript, or only in the title, or abstract and title, for example.
The findings are valid according to the design and objectives of this review. However, it leaves behind many other aspects that would be the focus of future research in the field. This review could benefit from having a broader coverage of those aspects, and not being reduced to transdermal methods and TDP1 fusion EGP proteins.
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