Background: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder which results in disruption to hormone production in adrenal cortex. There are multiple hydroxylase and lyase enzymes which are responsible for hormone conversion at different stages of the steroid biosynthesis pathway. A loss of function in one of the genes that encodes for these enzymes, results in CAH. Inadequate hormone production needs hormone replacement at regular intervals. However, this replacement can not meet the demand of periodic secretion especially in stress. Ultimately, these short-term treatments may cause metabolic disturbances and adrenal crisis. Hence, there is an extreme requisite of alternate solutions for long-time treatment of CAH. Gene based therapies attracts significant attention due to its lifelong effectiveness in which mutated gene is replaced by normal gene using vector system. While AAVrh10 has previously shown to have successful delivery to adrenal cortex, its delivery was short term. While this demonstrates proof of principle for adrenal gene delivery, enhanced targeting and improved longevity needs further investigation.
Methods: To determine if alternative AAV serotypes can target the adrenal cortex we assessed four different AAV serotypes to deliver green fluorescence protein (GFP) to determine cargo delivery efficiency to adrenal cortex. In this experiment, genes encode for GFP were encapsulated in AAV and injected into mice. After two weeks, tissues were collected, morphology and immunohistochemistry were performed to analyse GFP accumulation and biodistribution.
Results: Our preliminary data shows successful GFP delivery in adrenocortical cells in all serotypes analysed with a greater efficiency from what been previously described. Adrenal morphology is found to be normal when compared to control tissues indicating that AAVs are biocompatible for such treatments.
Conclusion: This data demonstrates novel AAV serotypes capable of delivering genetic cargo to the adrenal cortex, opening utility for improved gene therapies for the adrenal, and CAH disorders.