{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T13:19:59Z","timestamp":1769001599367,"version":"3.49.0"},"reference-count":143,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Reverse Rett","award":["RE16403"],"award-info":[{"award-number":["RE16403"]}]},{"name":"Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre","award":["RE16403"],"award-info":[{"award-number":["RE16403"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This systematic review and thematic analysis critically evaluated gene therapy trials in amyotrophic lateral sclerosis, haemoglobinopathies, immunodeficiencies, leukodystrophies, lysosomal storage disorders and retinal dystrophies and extrapolated the key clinical findings to individuals with Rett syndrome (RTT). The PRISMA guidelines were used to search six databases during the last decade, followed by a thematic analysis to identify the emerging themes. Thematic analysis across the different disorders revealed four themes: (I) Therapeutic time window of gene therapy; (II) Administration and dosing strategies for gene therapy; (III) Methods of gene therapeutics and (IV) Future areas of clinical interest. Our synthesis of information has further enriched the current clinical evidence base and can assist in optimising gene therapy and gene editing studies in individuals with RTT, but it would also benefit when applied to other disorders. The findings suggest that gene therapies have better outcomes when the brain is not the primary target. Across different disorders, early intervention appears to be more critical, and targeting the pre-symptomatic stage might prevent symptom pathology. Intervention at later stages of disease progression may benefit by helping to clinically stabilise patients and preventing disease-related symptoms from worsening. If gene therapy or editing has the desired outcome, older patients would need concerted rehabilitation efforts to reverse their impairments. The timing of intervention and the administration route would be critical parameters for successful outcomes of gene therapy\/editing trials in individuals with RTT. Current approaches also need to overcome the challenges of MeCP2 dosing, genotoxicity, transduction efficiencies and biodistribution.<\/jats:p>","DOI":"10.3390\/ijms24109023","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:35:11Z","timestamp":1684492511000},"page":"9023","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders\u2014Implications for Individuals with Rett Syndrome: A Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"given":"Jatinder","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London and South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Goodman-Vincent","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London and South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4830-5893","authenticated-orcid":false,"given":"Paramala","family":"Santosh","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AF, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"},{"name":"Centre for Interventional Paediatric Psychopharmacology (CIPP) Rett Centre, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London and South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/nature24058","article-title":"Radically truncated MeCP2 rescues Rett syndrome-like neurological defects","volume":"550","author":"Tillotson","year":"2017","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/nn.3434","article-title":"Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR\/SMRT co-repressor","volume":"16","author":"Lyst","year":"2013","journal-title":"Nat. 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