In vivo gene transfer of insulin gene into neonatal rats by the HVJ-liposome method resulted in sustained transgene expression.

In Many areas of disease such as homozygous familial hypercholesterolemia, no known effective therapy exists. The time is ripe for the introduction of gene therapy for the management of incurable disorders. However, for clinical gene therapy it is necessary to establish an efficient and non toxic gene delivery system. Recently, we have developed a gene delivery system mediated by Sendai virus as a potential means of gene therapy. However, this HVJ-liposome method has some disadvantages: (1) transient transgene expression; and (2) no integration. In gene therapy, it is desirable for transgenes to be expressed for as long as possible. To deal with this issue, we hypothesized that gene transfer into newborn animals would result in sustained expression of transgene. Our results demonstrated that transgene expression in liver was subsequently sustained for at least up to 8 weeks, as detected by reverse transcriptase PCR and radioimmunoassay, while our previous studies documented that transgene expression in adult animals disappeared within 2 weeks. Interestingly, we detected the presence of transgene in the host genomic DNA extracted from the nuclei of hepatic cells assessed by PCR. These findings provide new important information for gene therapy, although the mechanisms of sustained transgene expression are not clear.