Publications by authors named "Alessia De Caneva"
(AAV)-mediated episomal gene replacement therapy for monogenic liver disorders is currently limited in pediatric settings due to the loss of vector DNA, associated with hepatocyte duplication during liver growth. Genome editing is a promising strategy leading to a permanent and specific genome modification that is transmitted to daughter cells upon proliferation. Using genome targeting, we previously rescued neonatal lethality in mice with Crigler-Najjar syndrome.
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- - The study investigates using integrative gene therapy to treat hemophilia B in mouse models, showing that AAV8 vectors can effectively deliver the human coagulation factor IX (hFIX) gene and maintain elevated hFIX levels for at least 10 months in neonatal mice.
- - A single injection not only led to stable hFIX expression but also restored normal clotting capabilities in young FIX knockout mice, indicating a successful correction of the disease phenotype.
- - While the same approach in adult mice resulted in detectable hFIX levels, it was insufficient to meaningfully reduce bleeding risk, highlighting differences in gene therapy efficacy based on the age of the subjects.
Non-integrative AAV-mediated gene therapy in the liver is effective in adult patients, but faces limitations in pediatric settings due to episomal DNA loss during hepatocyte proliferation. Gene targeting is a promising approach by permanently modifying the genome. We previously rescued neonatal lethality in Crigler-Najjar mice by inserting a promoterless human uridine glucuronosyl transferase A1 (UGT1A1) cDNA in exon 14 of the albumin gene, without the use of nucleases.
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- - Crigler-Najjar syndrome type I (CNSI) is a rare genetic disorder causing severe jaundice in newborns, leading to high risks of neurological damage and death, with liver transplantation as the only current cure.
- - Researchers used a gene-targeting method to insert a therapeutic gene into a specific location in a mouse model of CNSI, successfully preventing neonatal death and significantly lowering bilirubin levels for over a year.
- - The treated mice exhibited normal liver function and motor skills, demonstrating that the gene therapy effectively addressed the disease, making it a promising option for CNSI treatment.
The Crigler-Najjar Syndrome Type I (CNSI) is a rare genetic disorder caused by mutations in the Ugt1a1 gene. It is characterized by unconjugated hyperbilirubinemia that may result in severe neurologic damage and death if untreated. To date, liver transplantation is the only curative treatment.
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