Naslov
Life-long liver specific AAV-mediated gene therapy in a Crigler-Najjar mouse model

Autori
Bortolussi, Giulia ; Bockor, Luka ; Zentilin, Lorena ; Mancarella, Antonio ; Bellarosa, Cristina ; Giacca, Mauro ; Tiribelli, Claudio ; Muro, Andrés Fernando

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

Skup
Telethon Congress

Mjesto i datum
Riva del Garda, Italija, 11.03.2013. - 13.03.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Crigler–Najjar syndrome type I, UGT1A1, neurological damage, AAV liver-specific gene therapy, mouse model

Sažetak
We demonstrated that a single neonatal hUGT1A1 gene transfer was successful and the therapeutic effect lasted up to 17 months postinjection. We also compared the efficacy of two different gene therapy approaches: liver versus skeletal muscle transgene expression. We observed that 5–8% of normal liver expression and activity levels were sufficient to significantly reduce bilirubin levels and maintain lifelong low plasma bilirubin concentration (3.1±1.5 mg/dl). In contrast, skeletal muscle was not able to efficiently lower bilirubin (6.4±2.0 mg/dl), despite 20–30% of hUgt1a1 expression levels, compared with normal liver. Our data support the concept that liver is the best organ for efficient and long- term CNSI gene therapy, and suggest that the use of extra-hepatic tissues should be coupled to the presence of bilirubin transporters.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija

POVEZANOST RADA