Naslov
Genome editing of a mouse model of the Crigler- Najjar Syndrome

Autori
Bočkor, Luka ; De Caneva, Alessia ; Porro, Fabiola ; Muro, Andrés Fernando

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy Collaborative Congress 2013 : abstracts ; u: Human gene therapy 24 (2013) 12 ; A1-A172 / - , 2013, A85-A86

Skup
The European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy Collaborative Congress

Mjesto i datum
Madrid, Španjolska, 25.10.2013. - 28.10.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Crigler-Najjar Syndrome, unconjugated hyperbilirubinemia, UGT1A1, TALEN, mouse hepatoma cell line, genome editing

Sažetak
Crigler-Najjar Syndrome (CNSI) is a rare genetic recessive disorder characterised by extreme unconjugated hyperbilirubinemia, caused by UDP- glucuronosyltransferase 1A1 (UGT1A1) deficiency. High blood levels of unconjugated bilirubin can lead to severe brain damage known as bilirubin encephalopathy or, in extreme cases, death by kernicterus. Presently, the only known treatments are intensive phototherapy, the efficacy of which decreaseswith time, and liver transplantation, a procedure that is not devoid of severe complications. In order to search for new therapies we are using a mouse model of the human CNSI that has a one-base deletion in the exon 4 of the mouse Ugt1 (mUgt1) gene, resulting in a stop codon immediately downstream of the mutation. Mutant mice have high bilirubin levels and die a few days after birth if left untreated. Recent advances in the field of sitespecific nucleases have made genome editing possible, reaching a previously unpredictadly high frequency. As only 5–10% of normal physiological levels of UGT1A1 are sufficient to reduce bilirubin levels to life-compatible levels, we devised in vivo and ex vivo strategies to repair the mutated gene. To this end we designed Transcription Activator-Like Effector Nucleases (TALENs) that target the mutated exon 4. We first verified their efficacy by targeting the exon 4 ofmUgt1a1 inNMuLi mouse hepatoma cell line. To increase the efficiency of exon 4 gene editing, we are using TALENs and oligonucleotides to repair the mutation by homology directed repair, both in vivo and ex vivo.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

Napomena
DOI: 10.1089/hum.2013.2513

POVEZANOST RADA