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Our research focuses on the development of gene and cell-based therapies for the treatment of metabolic diseases of the liver that commonly result in the development of intellectual disabilities in children. We have four active research directions:

1. Development of gene-based (adeno-associated virus, mRNA) therapies to restore nitrogen metabolism, ureagenesis, and creatine biosynthesis.
2. Exploring the underlying neurobiology in arginase deficiency and in guanidinoacetate methyltransferase deficiency to gain a greater understanding of the neuropathology that exists in these enzyme deficiencies.
3. Developing new therapeutic approaches to treating deficiency of carbamoyl phosphate synthetase 1.
4. Understanding the effect of guanidinoacetate on GABA-A receptors in guanidinoacetate methyltransferase deficiency.

Diep, T., Zhou, W., Reyes, R.E., Nitzahn, M., Day, I. L., Makris, G., Lueptow, L., Zhuravka, I., Bakshi, S., Gangoiti, J., Padaon, H., Li, Y., Barshop, B., Harberle, J., & Lipshutz, G. S. (2025). Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control. Molecular Therapy – Nucleic Acids, Volume 36, Issue 1. https://doi.org/10.1016/j.omtn.2025.102470

Nitzahn M, Allegri G, Khoja S, Truong B, Makris G, Häberle J, Lipshutz GS. Split AAV-Mediated Gene Therapy Restores Ureagenesis in a Murine Model of Carbamoyl Phosphate Synthetase 1 Deficiency. Mol Ther. 2020 Jul 8;28(7):1717-1730. doi: 10.1016/j.ymthe.2020.04.011.

Truong B, Allegri G, Liu XB, Burke KE, Zhu X, Cederbaum SD, Häberle J, Martini PGV, Lipshutz GS. Lipid nanoparticle-targeted mRNA therapy as a treatment for the inherited metabolic liver disorder arginase deficiency. Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21150-21159. doi: 10.1073/pnas.1906182116.