Report Summary

Toxicology and Biodistribution Study of rAAV-1-CB-hAAT in New Zealand White Rabbits

Study Summary

Overall Study Design 
The primary objective of this study was to determine if rAAV1-CB-hAAT vector sequences could be detected in the gonadal 
tissue of male rabbits following a single intramuscular administration of the vector and thus determine the potential for 
vertical transmission To further investigate the potential for vertical transmission semen was also analyzed for vector 
specific sequences 
Additional tissues skeletal muscle brainliver and blood were analyzed for presence transmission of AAV1-CB-hAAT 
vector DNA sequences following administration of vector to investigate vector spread and clearance from blood These 
objectives were accomplished by examination of the genomic DNA gDNA by PCR The skeletal muscle front brain liver 
and gonads were also examined using standard histopathalogical techniques 
A previous toxicology and biodistribution study in mice 02UF03MAAT with recombinant Adeno-Associated Virus Serotype 
1 human alpha-1 antitrypsin rAAV1-CB-hAAT demonstrated the distribution of vector following intramuscular injection to 
the gonadal tissue at the high dose 1 x 10e13 vector genomes administered in the study The purpose of this study is to 
further evaluate the toxicology and biodistribution of rAAV1-Cb-hAAT following intramuscular injection ov vector into male 
New Zealand White Rabbits Of particular interest is examination of the potential for germ line transmission of vector 
sequences through the semen 
The study consisted of 5 groups of rabbits which were all injected under Doppler ultrasound guidance a contrtol group 
where rabbits received only vehicle the test article treated groups where rabbits received one of the three different doses of 
rAAV1-CB-hAAT 3 x 10e12 vg 1 x 10e13 vg and 4 x 10e13 vg and a fifth control group that received only 
rAAV1-CB-UF11 identical to rAAV1-CB-hAAT excpet that the hAAT gene is replaced by the green fluorescent protein 
GFP gene 3 x 10e12 vg the purpose of the UF11 group was to identify any technical complications that might be 
encountered during vector administration of test article treated animals Animals were sacrificed 21 days 60 days and 90 
days after the injection date 
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