Title: High density CDNA arrays for the characterisation of mucosal gene expression in inflammatory bowel disease
Abstract: Recombinant adenoviruses are highly efficient gene transfer vehicles but their administration to mammalians is accompanied by strong inflammatory response.The present study reports additional side effects observed during adenoviral gene transfer studies in rabbits.Hematological and serological parameters.the course of viremia and the organ distribution were analyzed after in vivo administration of EI-deleted adenoviruses in rabbits.In addition.we tested hemagglutination patterns of crude and purified virus preparations of four different E I-deleted recombinant serotype 5 adenoviruses and that of wildtype with human, rat, mice.and rabbit derived erythrocyte preparations.The systemic administration of a therapeutic dose of 5x I0" infectiou s particles/kg (infusion time 20 min) led to an average reduction of 80-90% in the platelet count within 48 h.Full recovery took 10-14 days.Virus administration induced a strong but transient erythroblastosis (peaking 24 h after administration) which settled 48 h later.Normochromic anemia occured over the next 10 days with hemoglobin levels dropping by about 40 % to reach the lowest level 10 days after administration and taking two months for full recovery.In order to test the species specific reaction, we also evaluated mice.Dose-dependent thrombocytopenia was also found in mice, but neither erythroblasto sis nor anemia was observed (in equivalent doses).The hematological findings did not improve after local injection via the portal vein.Local and systemic administration led to a comparable course of viremia .Only minor differences were found in the biodistribut ion of viruses between local and systemic administration.Large amounts of viral DNA and transgene expression were found in the lungs, the kidneys and the ovaries.even after local administration via the portal vein.Local intravenous injection via the portal vein does not prevent systemic spread of viral vectors and the occurence of vector-related side effects.We also tested the hemagglutination properties of recombinant serotype 5 adenoviruses.None of the purified serotype 5 viruses showed hemagglutination with rabbit or mice erythrocytes but partial hemagglutination in rat erythrocytes.The hematological changes in the presence of adenoviruses suggest the need for carefu l monitoring of hematological and rheological parameters in clinical trials.5171