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GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy

Interest in gene-based therapies for neurodevelopmental disorders is increasing exponentially, driven by the rise in recognition of underlying genetic etiology, progress in genomic technology, and recent proof of concept in several disorders. The current prioritization of one genetic disorder over a...

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Autores principales: Chopra, Maya, Modi, Meera E., Dies, Kira A., Chamberlin, Nancy L., Buttermore, Elizabeth D., Brewster, Stephanie Jo, Prock, Lisa, Sahin, Mustafa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478871/
https://www.ncbi.nlm.nih.gov/pubmed/36156879
http://dx.doi.org/10.1016/j.omtm.2022.08.007
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author Chopra, Maya
Modi, Meera E.
Dies, Kira A.
Chamberlin, Nancy L.
Buttermore, Elizabeth D.
Brewster, Stephanie Jo
Prock, Lisa
Sahin, Mustafa
author_facet Chopra, Maya
Modi, Meera E.
Dies, Kira A.
Chamberlin, Nancy L.
Buttermore, Elizabeth D.
Brewster, Stephanie Jo
Prock, Lisa
Sahin, Mustafa
author_sort Chopra, Maya
collection PubMed
description Interest in gene-based therapies for neurodevelopmental disorders is increasing exponentially, driven by the rise in recognition of underlying genetic etiology, progress in genomic technology, and recent proof of concept in several disorders. The current prioritization of one genetic disorder over another for development of therapies is driven by competing interests of pharmaceutical companies, advocacy groups, and academic scientists. Although these are all valid perspectives, a consolidated framework will facilitate more efficient and rational gene therapy development. Here we outline features of Mendelian neurodevelopmental disorders that warrant consideration when determining suitability for gene therapy. These features fit into four broad domains: genetics, preclinical validation, clinical considerations, and ethics. We propose a simple mnemonic, GENE TARGET, to remember these features and illustrate how they could be scored using a preliminary scoring rubric. In this suggested rubric, for a given disorder, scores for each feature may be added up to a composite GENE TARGET suitability (GTS) score. In addition to proposing a systematic method to evaluate and compare disorders, our framework helps identify gaps in the translational pipeline for a given disorder, which can inform prioritization of future research efforts.
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spelling pubmed-94788712022-09-22 GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy Chopra, Maya Modi, Meera E. Dies, Kira A. Chamberlin, Nancy L. Buttermore, Elizabeth D. Brewster, Stephanie Jo Prock, Lisa Sahin, Mustafa Mol Ther Methods Clin Dev Review Interest in gene-based therapies for neurodevelopmental disorders is increasing exponentially, driven by the rise in recognition of underlying genetic etiology, progress in genomic technology, and recent proof of concept in several disorders. The current prioritization of one genetic disorder over another for development of therapies is driven by competing interests of pharmaceutical companies, advocacy groups, and academic scientists. Although these are all valid perspectives, a consolidated framework will facilitate more efficient and rational gene therapy development. Here we outline features of Mendelian neurodevelopmental disorders that warrant consideration when determining suitability for gene therapy. These features fit into four broad domains: genetics, preclinical validation, clinical considerations, and ethics. We propose a simple mnemonic, GENE TARGET, to remember these features and illustrate how they could be scored using a preliminary scoring rubric. In this suggested rubric, for a given disorder, scores for each feature may be added up to a composite GENE TARGET suitability (GTS) score. In addition to proposing a systematic method to evaluate and compare disorders, our framework helps identify gaps in the translational pipeline for a given disorder, which can inform prioritization of future research efforts. American Society of Gene & Cell Therapy 2022-08-29 /pmc/articles/PMC9478871/ /pubmed/36156879 http://dx.doi.org/10.1016/j.omtm.2022.08.007 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Chopra, Maya
Modi, Meera E.
Dies, Kira A.
Chamberlin, Nancy L.
Buttermore, Elizabeth D.
Brewster, Stephanie Jo
Prock, Lisa
Sahin, Mustafa
GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title_full GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title_fullStr GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title_full_unstemmed GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title_short GENE TARGET: A framework for evaluating Mendelian neurodevelopmental disorders for gene therapy
title_sort gene target: a framework for evaluating mendelian neurodevelopmental disorders for gene therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478871/
https://www.ncbi.nlm.nih.gov/pubmed/36156879
http://dx.doi.org/10.1016/j.omtm.2022.08.007
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