Peer Review History

Original SubmissionApril 6, 2023
Decision Letter - Jian Xu, Editor

PONE-D-23-10026Controlled and customizable baculovirus NOS3 gene delivery using PVA-based hydrogel systems.PLOS ONE

Dear Dr. Prakash,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Jian Xu, Ph.D.

Academic Editor

PLOS ONE

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"YES. This work was supported by a grant from the Canadian Institute of Health Research (CIHR) to Dominique Shum-Tim and Satya Prakash. S.S. is fully funded by the Canadian Graduate Scholarship-Doctoral from the Natural Sciences and Engineering Research Council (NSERC). P.I. is funded by the Islamic Development Bank Scholarship (2020-245622). A.A. is fully funded by a scholarship from the Ministry of Higher Education of the Arab Republic of Egypt. R.T. and K.A. are funded by the Canadian Graduate Scholarship-Master’s from NSERC."

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study provides important insights into the potential of NOS3 eluting PVA-based hydrogels for medical applications and device coatings. The addition of gelatin to the hydrogels is shown to be effective in protecting baculovirus viability and enabling sustained release. However, the study has limitations in terms of investigating the actual effects of NOS3 delivery on cell proliferation, blood vessel vasodilation, and bacterial growth inhibition, as well as providing detailed characterization of the properties of the hydrogels. Nevertheless, the study has value in providing a proof of concept for a potential delivery system and highlights areas for further research and development.

The study only investigates the release of baculoviruses and their potential for NOS3 gene delivery. It does not investigate the actual effect of NOS3 delivery on cell proliferation, blood vessel vasodilation, or bacterial growth inhibition.

The study only investigates the effect of hydrogel composition on properties such as elasticity, blood coagulation, and antimicrobial effects, but does not provide a detailed characterization of these properties.

The study does not investigate the long-term stability of the hydrogels or the effect of storage conditions on their properties and performance.

Reviewer #2: This manuscript evaluates the use of hydrogel formulations for sustained delivery of baculovirus in a proof-of-concept study. The manuscript is well written, properly illustrated and appropriately referenced. The result stand on their own. Baculovirus as a vehicle for gene delivery and gene editing is increasingly gaining interest and traction due to the numerous advantages of this viral vector above the state-of-the-art. This study represents and interesting and insightful contribution that will be valuable for the field.

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Reviewer #1: No

Reviewer #2: No

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Revision 1

PONE-D-23-10026 Editor & Reviewer Responses

Controlled and customizable baculovirus NOS3 gene delivery using PVA-based hydrogel systems

Dear Editor:

Thank you for your advice and recommendations. We appreciate the opportunity to revise manuscript. We have followed and completed all your recommendations. Briefly:

1. We have reformatted the manuscript and figure files to meet PLOS One’s requirements.

2. The funding information has been checked and should be as follows:

a. This work was supported by a grant from the Canadian Institute of Health Research (CIHR, grant 252743) to Dominique Shum-Tim and Satya Prakash. S.S. is fully funded by the Canadian Graduate Scholarship-Doctoral from the Natural Sciences and Engineering Research Council (NSERC, 569661-2022).). P.I. is funded by the Islamic Development Bank Scholarship (2020-245622). A.A. is fully funded by a scholarship from the Ministry of Higher Education of the Arab Republic of Egypt. R.T. and K.A. are funded by the Canadian Graduate Scholarship-Master’s from NSERC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

3. The statement has been added after the funding information provided in the manuscript.

4. The competing interests form has been completed, http://journals.plos.org/plosone/s/submit-now

5. Data availability statement: the minimal data underlying the results has been provided in the attached Excel sheet with each figure labelled.

6. Ethics approval was not required for the study and this statement has been added to the Methods section of the manuscript.

Reviewer #1

Comment: The study provides important insights into the potential of NOS3 eluting PVA-based hydrogels for medical applications and device coatings. The addition of gelatin to the hydrogels is shown to be effective in protecting baculovirus viability and enabling sustained release. However, the study has limitations in terms of investigating the actual effects of NOS3 delivery on cell proliferation, blood vessel vasodilation, and bacterial growth inhibition, as well as providing detailed characterization of the properties of the hydrogels. Nevertheless, the study has value in providing a proof of concept for a potential delivery system and highlights areas for further research and development.

The study only investigates the release of baculoviruses and their potential for NOS3 gene delivery. It does not investigate the actual effect of NOS3 delivery on cell proliferation, blood vessel vasodilation, or bacterial growth inhibition.

The study only investigates the effect of hydrogel composition on properties such as elasticity, blood coagulation, and antimicrobial effects, but does not provide a detailed characterization of these properties.

The study does not investigate the long-term stability of the hydrogels or the effect of storage conditions on their properties and performance.

Response: Thank you for your approval of the manuscript. We also appreciate your important suggestions. As per your suggestions and recommendations, we have revised this manuscript. You will find we have addressed all your concerns. Briefly:

The effect of NOS3 delivery on both HUVEC and SMC proliferation is presented in Figure 4e-f. We have also added a Griess assay to measure nitrate concentration (Figure 4d). An antibacterial assay using NOS3 and nitrate has been added. Moreover, previous papers have already established NOS3 and nitric oxide as a cardiovascular support and antimicrobial properties and have been cited in lines 470-478.

Further details have also been added for the hydrogel swelling, antimicrobial effects, and blood coagulation on pages 13-14.

The long-term stability was added to lines 456-460 and 334-335.

Storage conditions of the baculovirus-eluting hydrogels have been added to lines 456-460.

Reviewer #2:

This manuscript evaluates the use of hydrogel formulations for sustained delivery of baculovirus in a proof-of-concept study. The manuscript is well written, properly illustrated and appropriately referenced. The result stand on their own. Baculovirus as a vehicle for gene delivery and gene editing is increasingly gaining interest and traction due to the numerous advantages of this viral vector above the state-of-the-art. This study represents and interesting and insightful contribution that will be valuable for the field.

Response: Thank you for your acceptance and recommendation of the article for publication.

Attachments
Attachment
Submitted filename: PONE-D-23-10026 reviewer responses.docx
Decision Letter - Jian Xu, Editor

Controlled and customizable baculovirus NOS3 gene delivery using PVA-based hydrogel systems.

PONE-D-23-10026R1

Dear Dr. Prakash,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Jian Xu, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed the comments. The manuscript can be considered for publication in its present form.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

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Formally Accepted
Acceptance Letter - Jian Xu, Editor

PONE-D-23-10026R1

Controlled and customizable baculovirus NOS3 gene delivery using PVA-based hydrogel systems

Dear Dr. Prakash:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Jian Xu

Academic Editor

PLOS ONE

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