Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript " Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation’’ addresses an important and emerging topic. The manuscript is well-structured, with strong coverage of gene-editing strategies in DMD. However, the authors need to clarify some important points for better acceptability of the manuscript

After going through the manuscript, I have following comments for the authors:

1. The novelty of the study needs to be better clarified and articulated. Please discuss what explicitly distinguishes this review from previous studies (e.g., integration of translational barriers? comparison across editing platforms?). Also discuss whether the study offers a systematic comparison, clinical focus, or future roadmap. A short paragraph at the end of Introduction section clarifying these points is suggested.
2. The manuscript is mostly descriptive, especially in sections on CRISPR, base editing, and prime editing. Please consider adding more critical evaluation, for example: comparison of efficiencies across strategies (not just listing results), more quantitative discussion of limitations (editing %, delivery constraints, toxicity), and documentation of conflicting findings wherever relevant.
3. The preclinical data is sufficiently covered. However, the discussion on clinical translation is relatively brief and scattered. Please expand on ongoing or completed known clinical trials, regulatory challenges, and real-world barriers (manufacturing, cost, scalability).
4. The manuscript is largely well-written. Still, there are many long and clumsy sentences. Please consider streamlining the draft with simple and short sentences for better readability.
5. Some terminologies are inconsistently used:

“CRISPR/Cas9” vs “CRISPR-Cas9”

“sgRNA” vs “guide RNA”

“DMD gene” vs “dystrophin gene”

Please double check the manuscript for such inconsistencies.

Comments on the Quality of English Language

Language is fine. Still, some grammatical corrections and syntax adjustments are suggested. 

Author Response

The manuscript " Gene Editing Strategies for Duchenne Muscular Dystrophy: From Molecular Mechanisms to Clinical Translation’’ addresses an important and emerging topic. The manuscript is well-structured, with strong coverage of gene-editing strategies in DMD. However, the authors need to clarify some important points for better acceptability of the manuscript

After going through the manuscript, I have following comments for the authors:

Comment 1: The novelty of the study needs to be better clarified and articulated. Please discuss what explicitly distinguishes this review from previous studies (e.g., integration of translational barriers? comparison across editing platforms?). Also discuss whether the study offers a systematic comparison, clinical focus, or future roadmap. A short paragraph at the end of Introduction section clarifying these points is suggested.

Response 1:

We appreciate this important suggestion. We have now added a dedicated paragraph at the end of the Introduction to explicitly clarify the novelty of our review. In particular, we emphasize that this manuscript adopts a comparative and translational framework, focusing on (i) systematic comparison across gene-editing platforms, (ii) integration of translational barriers, and (iii) a decision-oriented perspective for therapeutic application. (See revised Introduction, Lines-78 to 90).

Comments 2. The manuscript is mostly descriptive, especially in sections on CRISPR, base editing, and prime editing. Please consider adding more critical evaluation, for example: comparison of efficiencies across strategies (not just listing results), more quantitative discussion of limitations (editing %, delivery constraints, toxicity), and documentation of conflicting findings wherever relevant.

Response 2:

We have substantially revised the manuscript to reduce descriptive content and incorporate critical and comparative analysis. Specifically:

Editing strategies (CRISPR, base editing, prime editing) are now discussed in terms of efficiency, limitations, and applicability, rather than simple listing of studies. We also highlight limitations and, where relevant, variability across studies.

Comments 3. The preclinical data is sufficiently covered. However, the discussion on clinical translation is relatively brief and scattered. Please expand on ongoing or completed known clinical trials, regulatory challenges, and real-world barriers (manufacturing, cost, scalability).

Response 3:

We have expanded and reorganized the section on clinical translation. It now includes:

Discussion of ongoing and recent clinical trials, Consideration of regulatory and safety challenges, Practical barriers such as manufacturing, cost, scalability, and systemic delivery

This section has been restructured to provide a more integrated translational perspective.

Comments 4. The manuscript is largely well-written. Still, there are many long and clumsy sentences. Please consider streamlining the draft with simple and short sentences for better readability.

Response 4:

We have carefully edited the manuscript to improve readability by: Shortening long sentences, Simplifying complex phrasing, Improving overall flow and clarity throughout the text.

1. Some terminologies are inconsistently used:

“CRISPR/Cas9” vs “CRISPR-Cas9”

“sgRNA” vs “guide RNA”

“DMD gene” vs “dystrophin gene”

Please double check the manuscript for such inconsistencies.

Response 5:

We have revised the manuscript to ensure consistent terminology throughout. Specifically:

• Standardized usage of CRISPR/Cas9
• Unified use of sgRNA (with initial definition as guide RNA)
• Consistent reference to the DMD (dystrophin) gene

Reviewer 2 Report

Comments and Suggestions for Authors

This review article about DMD is very well written and really interesting to read! I suggest only some minor points:

1.) Please add a relevant OMIM identifier for DMD.

2.) Please explain all abbreviations, which you use them the first time. e.g. CRISPR (Line 19) or HITI (line 21).

3.) Introduction: Please indicate and explain also the heart phenotype of Duchenne patients. 

4.) It would be great if the authos can summary the different gene editing tools like base editors or prime editors in an additional schematic figure.

In summary, I suggest a minor revision for this nice review article.

Author Response

This review article about DMD is very well written and really interesting to read! I suggest only some minor points:

Comments 1. Please add a relevant OMIM identifier for DMD.

Response 1:
We have added the OMIM identifier for DMD in the Introduction section. (OMIM: #310200). Please see lines 43.

Comments 2. Please explain all abbreviations, which you use them the first time. e.g. CRISPR (Line 19) or HITI (line 21).

Response 2:
All abbreviations (e.g., CRISPR, HITI) are now defined at first occurrence in the manuscript.

Comments 3: Introduction: Please indicate and explain also the heart phenotype of Duchenne patients. 

Response 3:
We have expanded the Introduction to include a brief description of the cardiac phenotype in DMD, including cardiomyopathy and its clinical significance.

Comments 4. It would be great if the authos can summary the different gene editing tools like base editors or prime editors in an additional schematic figure.

Response 4:

We agree with this valuable suggestion and have added a schematic figure summarizing major gene-editing strategies, including CRISPR-based editing, base editing, and prime editing, to improve clarity and visualization. Please see figure-2

We thank the reviewers again for their constructive feedback. We believe that the revisions have significantly improved the manuscript in terms of novelty, clarity, and translational relevance, and we hope it is now suitable for publication.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for addressing my comments. I am happy with your response.

Comments on the Quality of English Language

Language is fine. Still, some grammatical corrections and syntax adjustments are suggested.