Durable tissue-specific transgene expression in newborn mice following intraperitoneal delivery of non-cytotoxic HSV vectors.

This report describes the distribution and transgene expression of two non-cytotoxic, replication-defective (rd) herpes simplex virus (HSV) vectors, JΔNI7 and JΔNI8, following intraperitoneal delivery to newborn mice. The two vectors are functionally defective for all immediate-early genes, and JΔNI8 is further deleted for the UL41 endonuclease (). Both vectors were engineered to express a red luciferase gene from the LAT locus to track vector distribution and gene expression . A comparison of reporter gene activities under the control of four different promoters in JΔNI7 showed that the strongest expression was achieved with the CAG promoter. Distribution analysis at 1 week post-injection showed transgene expression in multiple tissues, but at 4 weeks, high-level expression was limited to the spinal cord, skin, and muscles. JΔNI8 showed rapid clearance of vector DNA in most tissues, suggesting a role for the gene in vector stability. Compared with wild-type KOS strain injections, JΔNI7-based non-cytotoxic rdHSV did not induce substantial CD45 immune-cell infiltration or tissue destruction, suggesting that our rdHSV vectors are safe. Taken together, these results demonstrate tissue-specific, durable transgene expression following systemic delivery of rdHSV vectors, suggesting their potential for systemic gene therapy for newborns with skin or neuromuscular diseases.