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Review
Peer-Review Record

Hematopoietic Stem Cell Gene-Addition/Editing Therapy in Sickle Cell Disease

Cells 2022, 11(11), 1843; https://doi.org/10.3390/cells11111843
by Paula Germino-Watnick 1,*,†, Malikiya Hinds 1,†, Anh Le 1,†, Rebecca Chu 1,†, Xiong Liu 1,† and Naoya Uchida 1,2,*
Reviewer 1:
Reviewer 2:
Cells 2022, 11(11), 1843; https://doi.org/10.3390/cells11111843
Submission received: 15 April 2022 / Revised: 29 May 2022 / Accepted: 2 June 2022 / Published: 4 June 2022
(This article belongs to the Special Issue Novel Approaches in Hematopoiesis Research)

Round 1

Reviewer 1 Report

This review manuscript describing the cure method for sickle cell disease mainly using HSC gene-addition/editing is very interesting and contains various information regarding to these methods per se, and their clinical trials. The authors described gene-addition/editing in detail, which will be understandable for all readers including unexperienced researchers. Thus the manuscript is well written, I have a few comments.

Line 139, efficient gene marking in CD34+ cells → What gene? Also in line 173, gene marking levels, does this gene mean added gene?

Line 194, is SIN an abbreviation?

Lines 232-235, I could not understand what the authors would like to mention.  How robust engraftment of HSCs with high-level gene marking is important to maintain polyclonal hematopoiesis?

 

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

 

The manuscript of Germino-Watnick et al. with the title "Hematopoietic stem cell gene-addition/editing therapy in sickle cell disease" presents an informative study that aims to describe the prospects of HSC gene therapy for SCD and β-thalassemia. This study is descriptive, detailed, and provides key details in the field of gene therapy.  However, there are several minor issues that need to be addressed:

·       The authors are advised to provide additional information with regard to the reason for which they studied β-thalassemia and what it offers in terms of novelty.

·       Line 48: “Targeting γ-globin expression through its regulatory elements such as BCL11A, is another approach for HSC editing”. It is suggested that the authors provide additional information on γ-globin regulatory elements and how they are involved in HSC editing.

·       “However, insertional mutagenesis remains a risk. Additionally, achieving long-term engraftment of gene-modified cells post-transplant can be challenging as culture conditions must adhere to certain guidelines”. The authors should mention how these limitations could be overcome.

·       The authors should clarify whether the combination of plerixafor/G-CSF is indicated in HSD patients or not.

·       In the third and fourth part, the authors describe the gene-editing techniques in detail. However, the authors need to highlight the technique with the most advantages for HSD.

·       Due to the text extensive length, the addition of figures, especially in part 3, would render the text more comprehensible.

·       Additional commentary could be added in the Conclusions, regarding the importance of gene editing in SCD and their potential utilization in standard clinical practice.

·       Proofreading of the manuscript is needed, since some syntax and grammar errors exist.

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

I do not have further comments.

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