SAFETY OF SALIVARY GLAND-ADMINISTERED REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS IN RATS

We have examined the safety of a replication-deficient recombinant ade novirus administered at a single, high dose intraductally to rat subma ndibular glands or systemically via the femoral vein. The virus used d irected the synthesis of human aquaporin-1, a water channel protein, a nd is termed AdhAQP1. Comparisons were made 1 and 9 days post-infectio n with animals administered either a similar virus encoding no transge ne or the viral suspension buffer. Animals were specifically not given anti-inflammatory drugs to impede the well-known immunopathologic res ponse to recombinant adenoviral administration. Serum chemistries and hematological parameters were monitored. Rats were subjected to comple te gross necropsy and selected tissues were evaluated by histopatholog y. Most clinical chemistry and hematology values were within normal ra nges; however, evidence of inflammation (e.g., elevated lactic dehydro genase, total leukocyte count) was seen. Gross pathology was normal, a s was histopathology, excepting rare focal areas of necrosis. The resu lts show that intrasalivary gland or intravenous AdhAQP1 administratio n leads to low levels of toxicity in rats.