TY  - JOUR
T1  - Genome editing in the adrenal gland: a novel strategy for treating congenital adrenal hyperplasia
AU  - van Dijk, Eva B.
AU  - Ginn, Samantha L.
AU  - Alexander, Ian E.
AU  - Graves, Lara E.
Y1  - 2024///
JO  - Exploration of Endocrine and Metabolic Diseases
VL  - 1
IS  - 3
SP  - 101
EP  - 121
DO  - 10.37349/eemd.2024.00011
UR  - https://www.explorationpub.com/Journals/eemd/Article/101411
AB  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency leads to high morbidity and mortality, despite the availability of life-saving corticosteroid replacement therapy. Gene therapy represents a promising potential treatment for monogenic disorders such as congenital adrenal hyperplasia, overcoming the limitations of corticosteroid replacement approaches. Adeno-associated viral vectors are currently the leading vector for direct in vivo gene delivery. However, physiological properties of the adrenal gland limit the application of adeno-associated viral vector-based gene addition strategies. To achieve durable correction in the adrenal gland, gene editing must be employed to stably introduce a genetic modification into the CYP21A2 locus. The safety of this and other gene editing approaches could be greatly improved by using lipid nanoparticles for the delivery of editing machinery mRNA. While little data exists regarding adrenocortical lipid nanoparticle targeting, physiological features of this organ (such as high relative blood flow, fenestrated endothelium, and cholesterol uptake) indicate the promise of these delivery vectors for the treatment of monogenic diseases of the adrenal cortex. This review discusses the complexities of developing gene therapy for congenital adrenal hyperplasia and explores the viability of novel gene therapy strategies in this application.
ER  -