AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia
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Le résumé fourni par la source
Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia; however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct in vivo gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalized, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia
- Date Crossref
- 01/06/2024
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The University of Sydney pays non établi dans la noticeUniversité ou école supérieure
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Children's Medical Research Institute pays non établi dans la noticeStructure de recherche
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Children's Hospital at Westmead NSW Newborn Screening Program pays non établi dans la noticeÉtablissement de santé
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Sydney Children’s Hospitals Network pays non établi dans la noticeÉtablissement de santé
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Faculty of Medicine and Health Sydney Medical School pays non établi dans la noticeUniversité ou école supérieure
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Institute of Endocrinology and Diabetes pays non établi dans la noticeStructure de recherche
The University of Sydney, Children's Medical Research Institute et NSW Newborn Screening Program — Children's Hospital at Westmead, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.