CELL DERIVED NANO-GHOSTS: A NOVEL TARGETED GENE DELIVERY SYSTEM FOR CANCER THERAPY

The clinical success of gene therapy is still overshadowed by considerable delivery and safety concerns that are mostly associated with the vectors used to induce transgene transfection. Besides being safe, an optimal vector for gene therapy should selectively target the cells of interest, be efficiently loaded with variety of constructs of different sizes, should not be immunogenic or immunotoxic, and should be produced using a scalable and cost effective process. Most of these traits, however, usually come one at the expanse of the other. We have developed membrane vesicles that both have inherent targeting capabilities and can be produced using a technologically scalable process. These vesicles, termed Nano-Ghosts (NGs), are produced from the cytoplasmatic membranes of mesenchymal stem cells (MSCs). The NGs are biocompatible and preserve the cells’ unique surface-associated targeting capabilities towards a variety of tumor cells. To demonstrate their applicability for gene therapy, NGs were loaded with cDNA encoding for PEX, a cancer toxic protein. NG-pPEX induced efficient transfection of prostate cancer cells leading to 40 and 50 fold increase in the PEX DNA and mRNA levels, respectively, compared to cell incubated with naked pPEX, and 7 fold increase in the PEX protein level. NG-pPEX transfection decreased the viability of prostate (PC3), lung (A549) and breast (MCF7) cancer cell lines for at least a week. The NGs demonstrated uncompromising in-vivo safety, leading to no off-target transfections, toxicity or immune response. NG therapy inhibited the growth of prostate tumor xenografts by almost 80% and doubled the animals’ survival. The NGs’ unprecedented safety, selectivity, and efficient transfection ability undeniably place them at the forefront of prospective gene-delivery technologies.