Gene Therapy for Childhood Neurofibromatosis

This high-risk, high-reward project was based on the observation that plexiform neurofibromas require a tumor microenvironment consisting of cells heterozygous for the neurofibromin NF1 gene. Cells with two functional alleles of NF1 did not support tumor growth. The treatment objective was therefore to increase the level of expression from the one active copy of NF1 to complement the haploinsufficiency in the cells of the tumor microenvironment. This was to be accomplished by designing artificial transcription factors ATFs. The ATFs were to be expressed from non-pathogenic, tumor-colonizing bacteria, which would introduce the ATF into the cells of the microenvironment. The hypothesis was that this treatment would ultimately halt or regress the tumors. Unfortunately the development of an active bacterial delivery vector was more difficult than we anticipated. While we were not able to complete all of the objectives outlined in the statement of work SOW within the one-year funding period, our data do indicate partial success in creating an ATF-bacterial delivery system.