Implications of AAV Serotypes in Neurological Disorders: Current Clinical Applications and Challenges

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The review article will be of interest to readers after significant revisions.
1) Discussion of Roctavian (valoctocogene roxaparvovec) is not appropriate in this article. This drug is approved for severe hemophilia A, but not for neurological diseases. I will mention Roctavian as an example of successful translation of research into practice.
2) The NCT04120493 (AMT-130) study does indeed target Huntington's disease, but uses AAV5 to deliver a microRNA targeting HTT (huntingtin), not "miHTT". The name "rAAV-miHTT" is used correctly in the text (line 179), but the vector number in the table is incorrect. 3) Table 2 lists "AAV2-GAD (NCT05603312)" for Parkinson's disease therapy, while the text on page 6 (line 150) mentions "AAV2-GAD for Parkinson's diseases (NCT04228653)".
4) The designation of vectors in tables should be carefully clarified and made uniform. For example, Table 2 uses a mixture of designations: "AAV2", "rAAV2", "AAV9", "rAAV9", "AAV"
5) The discussion of microglia is unclear. The text does not clearly link microglia to the discussion of clinical trials of drugs. The need for targeting microglia for the treatment of neurodegeneration should be clearly stated.
6) Page 3 (line 74) lists "~4.8 kb", while page 7 (line 203) lists "~4.7 kb".
7) The article contains many typos that spoil the overall impression of the text
8) The Future directions section should be expanded by indicating possible ways to overcome technical challenges (targeted delivery, nanotechnology, etc.)
9) It is necessary to strictly ensure that all abbreviations are deciphered at the first mention

Author Response

Dear Sir/Madam,

We thank you for your constructive feedback and providing necessary comments that has made important corrections and improved manuscript overall. We provide detailed manuscript attached here along with highlighted corrections in the manuscript. "Please see the attachment."

Sincerely,

Sachin Sharma

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is a very nice review paper. It is detailed and well organised. There are no major issues noted. Paper has well written introduction, advancement of AAV design, its clinical application in neurological disorders, current challenges, future directions and limitations. This will add to the literature as a good source to find and learn about AAV.

Author Response

Dear sir,

We thank you for your help and efforts in reviewing the manuscript.

Thanks,

Sachin

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have taken my comments into full account. The article can be accepted in its current form.