Details

Autor(en) / Beteiligte

• Roy, Soumitra
• Clawson, David
• Lebherz, Corinna
• Calcedo, Roberto
• Sanmiguel, Julio
• Wu, Di
• Wilson, James M

Titel

128. Use of chimeric adenoviral vectors to assess capsid neutralization determinants

Ist Teil von

• Molecular therapy, 2004-05, Vol.9 (S1), p.S50-S50

Ort / Verlag

Milwaukee: Elsevier Limited

Erscheinungsjahr

2004

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Use of adenoviral gene therapy vectors based on different non-cross reacting serotypes is being investigated by several groups as a means to administer adenoviral vectors, either in a re-administration setting, or in subjects with circulating antibodies against the common serotypes such as Ad2 or Ad5. We have previously developed GFP expressing vectors using the chimpanzee adenoviruses Pan 6 (C6-GFP) and Pan 7 (C7-GFP). We have determined that administration of either one of the two chimpanzee adenovirus vectors does not affect the transduction efficiency of the other vector while re-administration of the same vector is severely compromised. Adenoviruses have three major capsid proteins, hexon, penton base, and fiber, which elicit the production of circulating antibodies. We wished to elucidate the relative importance of each of the three capsid components in preventing transduction in a gene therapy setting. In order to do this we have generated a panel of GFP expressing vectors that are chimeric between Pan 6 and Pan 7 where the hexon protein or the fiber protein or both hexon and fiber proteins of the Pan 7 vector have been replaced by those from Pan 6. Balb/C mice were immunized with either Pan 6 or Pan 7 and re-administration (by tail vein injection) was attempted 3 weeks later using each of the five GFP expressing vectors (C6-GFP, C7-GFP, and the three chimeric vectors). Three days later the level of liver transduction was estimated qualitatively by examining liver sections for the presence of GFP expression and quantitatively by estimating copies of GFP DNA by Taqman analysis. The data showed that antibodies to both hexon and fiber are important in preventing re-administration of adenoviral vectors.