RGD Reference Report - In the rat liver, Adenoviral gene transfer efficiency is comparable to AAV. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

In the rat liver, Adenoviral gene transfer efficiency is comparable to AAV.

Authors: Montenegro-Miranda, PS  Pichard, V  Aubert, D  Ten Bloemendaal, L  Duijst, S  De Waart, DR  Ferry, N  Bosma, PJ 
Citation: Montenegro-Miranda PS, etal., Gene Ther. 2014 Feb;21(2):168-74. doi: 10.1038/gt.2013.69. Epub 2013 Nov 28.
RGD ID: 10769340
Pubmed: (View Article at PubMed) PMID:24285217
DOI: Full-text: DOI:10.1038/gt.2013.69

Adenoviral (AdV) and Adenovirus-associated viral (AAV) vectors both are used for in vivo gene therapy of inherited liver disorders, such as Crigler-Najjar syndrome type 1. In a relevant animal model, the Gunn rat, both vectors efficiently correct the severe hyperbilirubinemia characteristic of this liver disorder. Although the clinical use of AAV is more advanced, as demonstrated by the successful phase 1 trial in hemophilia B patients, because of its large cloning capacity AdV remains an attractive option. A direct comparison of the efficacy of these two vectors in the liver in a relevant disease model has not been reported. Aim of this study was to compare the efficiency of clinically applicable doses of both vectors in the Gunn rat. AdV or scAAV (self-complimentary AAV) ferrying identical liver-specific expression cassettes of the therapeutic gene, UGT1A1, were injected into the tail vein. As the titration methods of these two vectors are very different, a comparison based on vector titers is not valid. Therefore, their efficacy was compared by determining the amount of vector genomes delivered to the liver required for therapeutic correction of serum bilirubin. Like AAV, the liver-specific first-generation AdV also provided sustained correction in this relevant disease model. UGT1A1 mRNA expression provided per genome was comparable for both vectors. Flanking the expression cassette in AdV with AAV-ITRs (inverted terminal repeats), increased UGT1A1 mRNA expression eightfold which resulted in a significant improvement of efficacy. Compared with AAV, less AdV genomes were needed for complete correction of hyperbilirubinemia.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ugt1a1  (UDP glucuronosyltransferase family 1 member A1)

Genes (Mus musculus)
Ugt1a1  (UDP glucuronosyltransferase 1 family, polypeptide A1)

Genes (Homo sapiens)
UGT1A1  (UDP glucuronosyltransferase family 1 member A1)

Additional Information