Report Summary

Single Dose Biodistribution Study of AAV-CB-AAT Comparing IM and IV Routes of Vector Administration in the C57/B16 Mouse

Study Summary

Overall Study Design 
In the Biodistribution study rAAV-CB-hAAT was administered by the IM and IV routes This study was performed to 
demonstrate a worse case scenario where our gene therapy vector would inadvertently be administered intravenously as 
opposed to intramuscularly as intended The biodistribution study consisted of 2 groups each containing 4 experimental 
arms Each cohort of 4 mice 2m2f received a total dose of 1 x 107iu 3 x 108vg  12 x 1010vgkg 3 X 108iu 9 
x 109vg  36 x 1011vgkg  1 X 1010iu 3 x 1011vg  12 x 1012vgkg or 26 X 10 11 iu 8 x 1012vg  32 x 
1014vgkg of rAAV2-CB-hAAT One group was injected intramuscularly to mimic vector administration in a clinical setting
 The second group was injected with the same dose as the IM group but by intravenous administration An additional 
cohort of 4 mice received saline intramuscularly as a control All mice were sacrificed at 60 days post injection The 
primary safety endpoint of this study is the presence of vector genomes in the blood and the organs as listed above for the 
primary toxicology study Of primary question was the analysis of the presence of vector genomes in the gonad genomic 
DNA Vector genomes in the blood and organs were quantified by real-time PCR of extracted genomic DNA Histologic 
analysis was performed only on organs that were positive by PCR A small number of animals 1 PBS-IM injected control 
and 3 vector-IV injected animals had PCR signals from their gonad DNA the highest of which showed less than 200 copies 
per 01mg of DNA the amount used in the assay These data suggest a very low risk of gonadal gene transfer after IM 
administration of AAV-CB-AAT and a relatively low risk of gonadal transfer after IV administration 
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