Combined intraocular and intravenous gene delivery for therapy of gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina (GACR) is due to ornithine aminotransferase (OAT) deficiency, which causes hyperornithinemia, leading to retinal pigment epithelium, followed by choroidal and retinal degeneration. Adeno-associated virus serotype 8 (AAV8) vector-mediated OAT (AAV8-OAT) liver gene transfer reduces ornithinemia in the Oat mouse model of GACR and improves retinal function and structure. Since OAT is expressed in various tissues including the retina, we investigated the efficacy of restoration of OAT expression in either retina or liver or both tissues on the retinal phenotype of Oat mice.

Liver gene transfer for metabolite detoxification in inherited metabolic diseases.

Inherited metabolic disorders (IMDs) are a growing group of genetic diseases caused by defects in enzymes that mediate cellular metabolism, often resulting in the accumulation of toxic substrates. The liver is a highly metabolically active organ that hosts several thousands of chemical reactions. As such, it is an organ frequently affected in IMDs.

O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.

Life-threatening hyperammonemia occurs in both inherited and acquired liver diseases affecting ureagenesis, the main pathway for detoxification of neurotoxic ammonia in mammals. Protein O-GlcNAcylation is a reversible and nutrient-sensitive post-translational modification using as substrate UDP-GlcNAc, the end-product of hexosamine biosynthesis pathway. Here we show that increased liver UDP-GlcNAc during hyperammonemia increases protein O-GlcNAcylation and enhances ureagenesis.

Association between DNA methylation profile and malignancy in follicular-patterned thyroid neoplasms.

Molecular differentiation between benign (follicular thyroid adenoma, FTA) and malignant (follicular thyroid carcinoma, FTC) thyroid neoplasms is challenging. Here, we explored the genome-wide DNA methylation profile of FTA (n.10) and FTC (n.