Transfer of the CFTR Gene to the Lung of Nonhuman Primates with E1-Deleted, E2a-Defective Recombinant Adenoviruses: A Preclinical Toxicology Study

摘要: This paper describes a preclinical toxicology study designed to investigate the biological efficacy and safety profile of second-generation adenovirus for CFTR gene transfer into baboon lung. virus is deleted E1 contains temperature-sensitive mutation in E2a gene, which encodes defective DNA-binding protein. Two distinct projects were undertaken. Group A animals received first-generation (i.e., E1) an upper lobe at time was instilled contralateral lobe. The goal compare biology each construct directly determine if immune response affected performance virus. B lacZ same other Necropsies performed 4 or 21 days after tissues evaluated recombinant expression histopathology. Using adenovirus, stability prolonged associated with diminished level perivascular inflammation as compared vectors. Markedly levels hexon protein present infected No evidence viral shedding evident. Furthermore, coadministration first- did not affect transgene from These data suggest that adenoviral vectors provide improved delivery vehicle, thus may be useful therapy cystic fibrosis.