Abstract: Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a metabolic disorder of the liver that results m abnormal nitrogen metabolism. To illustrate the ability of gene therapy to treat CPS1 deficiency, two adeno-associated viruses encoding portions of a codon optimized CPS1 were generated and tested in a conditional CPS1 knock out mouse model. When administered to mice having knocked out endogenous CPS1 expression, mice from this model demonstrate homologous recombination and reconstitution of the codon optimized CPS1 gene, expression of the CPS1 protein and the associated control of plasma ammonia following the administered AAVs comprising the CPS1 gene sequences. While all control mice perish, the mice in this model live and have normal behavior. As there is no effective therapy for human patients with the CPS1 disorder, this invention can address this unmet need for these patients.

Abstract: Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a metabolic disorder of the liver that results m abnormal nitrogen metabolism. To illustrate the ability of gene therapy to treat CPS1 deficiency, two adeno-associated viruses encoding portions of a codon optimized CPS1 were generated and tested in a conditional CPS1 knock out mouse model. When administered to mice having knocked out endogenous CPS1 expression, mice from this model demonstrate homologous recombination and reconstitution of the codon optimized CPS1 gene, expression of the CPS1 protein and the associated control of plasma ammonia following the administered AAVs comprising the CPS1 gene sequences. While all control mice perish, the mice in this model live and have normal behavior. As there is no effective therapy for human patients with the CPS1 disorder, this invention can address this unmet need for these patients.