I heard about this medical breakthrough that connects to what I’ve been teaching about, so I thought I’d share in case you were interested. Basically, a baby was born with a CPS1 deficiency. That means he had a problem with one of the main enzymes of the urea cycle (carbamoyl-phosphate synthetase 1), that’s needed to safely dispose of nitrogen waste (as urea, not ammonia – no windex veins!). The deficiency is often fatal, so doctors at the Children’s Hospital of Pennsylvania treated the baby with the gene-editing tool CRISPR (which, by the way, was discovered through basic science research into bacterial immune systems) and now the baby is doing much better!
Penn press release: World’s First Patient Treated with Personalized CRISPR Therapy. https://www.pennmedicine.org/news/news-releases/2025/may/worlds-first-patient-treated-with-personalized-crispr-therapy?fbclid=IwY2xjawKW6-BleHRuA2FlbQIxMQBicmlkETFBdmIycVR6MDdjRzhjajRNAR4K0BajQkZ985aj0_opsILZ5pu_JFgGlp0mU6TC7STAtSZAF_fPVatGRC4cfw_aem_EBFMh_TEI1xNX5YP0xM8QQ (accessed 2025-05-19).
Musunuru, K. . . . Ahrens-Nicklas, R. C. et al. Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med 2025. https://doi.org/10.1056/nejmoa2504747.
More on CRISPR from me: http://bit.ly/crisprdoudna
More on amino acid metabolism and the urea cycle: https://youtu.be/Ce78en-LEcE & https://youtu.be/6X1uC6PDFmY
Urea cycle graphic: https://doi.org/10.5281/zenodo.14188989
More on CRISPR/Cas: https://bit.ly/crisprcasscience & https://youtu.be/sH6525d-A4s
Resources and references:
CRISPR 101: Cytosine and Adenine Base Editors. https://blog.addgene.org/single-base-editing-with-crispr (accessed 2025-05-17).
Pacesa, M.; Pelea, O.; Jinek, M. Past, Present, and Future of CRISPR Genome Editing Technologies. Cell 2024, 187 (5), 1076–1100. https://doi.org/10.1016/j.cell.2024.01.042.
Macarrón Palacios, A.; Korus, P.; Wilkens, B. G. C.; Heshmatpour, N.; Patnaik, S. R. Revolutionizing in Vivo Therapy with CRISPR/Cas Genome Editing: Breakthroughs, Opportunities and Challenges. Front. Genome Ed. 2024, 6. https://doi.org/10.3389/fgeed.2024.1342193.
Zhao, Z.; Shang, P.; Mohanraju, P.; Geijsen, N. Prime Editing: Advances and Therapeutic Applications. Trends in Biotechnology 2023, 41 (8), 1000–1012. https://doi.org/10.1016/j.tibtech.2023.03.004.
Anzalone, A. V.; Randolph, P. B.; Davis, J. R.; Sousa, A. A.; Koblan, L. W.; Levy, J. M.; Chen, P. J.; Wilson, C.; Newby, G. A.; Raguram, A.; Liu, D. R. Search-and-Replace Genome Editing without Double-Strand Breaks or Donor DNA. Nature 2019, 576 (7785), 149–157. https://doi.org/10.1038/s41586-019-1711-4.
Murray, J. B.; Harrison, P. T.; Scholefield, J. Prime Editing: Therapeutic Advances and Mechanistic Insights. Gene Ther 2025, 32 (2), 83–92. https://doi.org/10.1038/s41434-024-00499-1.
Chehelgerdi, M.; Chehelgerdi, M.; Khorramian-Ghahfarokhi, M.; Shafieizadeh, M.; Mahmoudi, E.; Eskandari, F.; Rashidi, M.; Arshi, A.; Mokhtari-Farsani, A. Comprehensive Review of CRISPR-Based Gene Editing: Mechanisms, Challenges, and Applications in Cancer Therapy. Molecular Cancer 2024, 23 (1), 9. https://doi.org/10.1186/s12943-023-01925-5.
Lazzarotto, C. R. et al. CHANGE-Seq-BE Enables Simultaneously Sensitive and Unbiased in Vitro Profiling of Base Editor Genome-Wide Activity. bioRxiv March 30, 2024, p 2024.03.28.586621. https://doi.org/10.1101/2024.03.28.586621.
Lichter-Konecki, U.; Caldovic, L.; Morizono, H.; Simpson, K.; Ah Mew, N.; MacLeod, E. Ornithine Transcarbamylase Deficiency. In GeneReviews®; Adam, M. P., Feldman, J., Mirzaa, G. M., Pagon, R. A., Wallace, S. E., Amemiya, A., Eds.; University of Washington, Seattle: Seattle (WA), 1993.
Longo, N.; and Holt, R. J. Glycerol Phenylbutyrate for the Maintenance Treatment of Patients with Deficiencies in Enzymes of the Urea Cycle. Expert Opinion on Orphan Drugs 2017, 5 (12), 999–1010. https://doi.org/10.1080/21678707.2017.1405807.
Diez-Fernandez, C.; Häberle, J. Targeting CPS1 in the Treatment of Carbamoyl Phosphate Synthetase 1 (CPS1) Deficiency, a Urea Cycle Disorder. Expert Opinion on Therapeutic Targets 2017, 21 (4), 391–399. https://doi.org/10.1080/14728222.2017.1294685.
