One application of Enzo's gene regulation platform, the company's proprietary StealthVector®HGTV43T transducing vector is a vehicle designed to carry and deliver anti-HIV-1 antisense RNA genes to autologous blood stem cells ex vivo (outside the body). These genes are incorporated into the DNA of the stem cells and engraft in the bone marrow where they replicate and produce progeny immune CD4 T cells containing the antisense RNA genes (engineered cells). In circulation the engineered cells have been shown to produce anti-HIV-1 antisense RNA which can prevent replication of the HIV virus.
Preclinical in vitro studies demonstrated resistance to HIV-1 in human immune cells into which the antisense genes had been inserted.
A Phase I human clinical trial of the StealthVector®HGTV43T was carried out on HIV-1-infected individuals. Results of the trial showed that:
Based on these Phase I trial results demonstrating long-term survival and functioning of antisense RNA in circulating immune cells, we initiated a PhaseI/II study, focusing on a strategy to increase the percentage of engineered immune cells in circulation. The first patient has undergone treatment and we are monitoring the progress.
- All subjects tolerated the procedure and that there were no treatment-related adverse events
- There was no evidence of expansion of the inserted transgenes in any subjects tested, nor was any evidence of leukemia seen by standard hematology;
- CD34+ cells from the bone marrow of all subjects were tested for the presence of anti HIV-1 antisense RNA between 8 months and 20 months after infusion and these cells contained the antisense RNA, indicating engraftment of the engineered cells;
- Anti-HIV-1 antisense RNA-containing immune cells were detected in the circulation of subjects, the longest at 72 months post-infusion