Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice
Abstract
:1. Introduction
2. Results
2.1. Combination of VTX-804 Administration with Nitrogen Scavenger Pretreatment Normalizes Survival and Weight Gain of Ass1fold Mice
2.2. VTX-804 Activates Ureagenesis in Ass1fold Mice and Improves CTLN1 Serum Biomarkers
2.3. VTX-804 Transduction Levels Diminish with Time
2.4. The Neurological Phenotype Developed by Ass1fold Mice Is Corrected by VTX-804 Treatment
2.5. Histological Brain Alterations Developed by Ass1fold Mice
3. Discussion
4. Materials and Methods
4.1. Cloning and Construction of rAAV Vector
4.2. Production of rAAV Vectors
4.3. Animal Studies
4.4. Analysis of Biochemical Parameters in Serum
4.5. Nucleic Acid Extraction and qPCR
4.6. Ureagenesis
4.7. Behavioural Studies
4.8. Immunofluorescence
4.9. Image Acquisition
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Bazo, A.; Lantero, A.; Mauleón, I.; Neri, L.; Poms, M.; Häberle, J.; Ricobaraza, A.; Bénichou, B.; Combal, J.-P.; Gonzalez-Aseguinolaza, G.; et al. Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice. Int. J. Mol. Sci. 2022, 23, 14940. https://doi.org/10.3390/ijms232314940
Bazo A, Lantero A, Mauleón I, Neri L, Poms M, Häberle J, Ricobaraza A, Bénichou B, Combal J-P, Gonzalez-Aseguinolaza G, et al. Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice. International Journal of Molecular Sciences. 2022; 23(23):14940. https://doi.org/10.3390/ijms232314940
Chicago/Turabian StyleBazo, Andrea, Aquilino Lantero, Itsaso Mauleón, Leire Neri, Martin Poms, Johannes Häberle, Ana Ricobaraza, Bernard Bénichou, Jean-Philippe Combal, Gloria Gonzalez-Aseguinolaza, and et al. 2022. "Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice" International Journal of Molecular Sciences 23, no. 23: 14940. https://doi.org/10.3390/ijms232314940