Viruses are popular delivery vehicles for gene therapy applications, but they suffer from numerous potential side effects. In order to bypass their use altogether, researchers at MIT and Lankenau Institute are developing nanoparticles that similarly can deliver the genes. Specifically, while targeting ovarian cancer, with the help of nanoparticles, the researchers implanted a suicide gene into cancer cells that forces them produce the diphtheria toxin, which in turn kills the tumor.
Anderson and others from MIT, including Institute Professor Robert Langer, along with researchers from the Lankenau Institute, led by Professor Janet Sawicki, found that the gene-therapy treatment was equally as effective, and in some cases more effective, than the traditional chemotherapy combination of cisplatin and paclitaxel. Furthermore, it did not have the toxic side effects of chemotherapy because the gene is engineered to be overexpressed in ovarian cells but is inactive in other cell types.
To further ensure tumor-focused effects, the nanoparticles were administered by injection into the peritoneal cavity, which encases abdominal organs such as the stomach, liver, spleen, ovaries and uterus. Ovarian cancer is known to initially spread throughout the peritoneal cavity, and current therapeutic approaches in humans include direct injection into the peritoneal space, thereby targeting the therapy to the ovaries and nearby tissues where tumors may have spread.
The new nanoparticles are made with positively charged, biodegradable polymers known as poly(beta-amino esters). When mixed together, these polymers can spontaneously assemble with DNA to form nanoparticles. The polymer-DNA nanoparticle can deliver functional DNA when injected into or near the targeted tissue.
For several years, the MIT-Lankenau team has been developing these nanoparticles as an alternative to viruses, which are associated with safety risks. In addition to ovarian cancer, these nanoparticles have demonstrated potential for treatment of a variety of diseases, including prostate cancer and viral infection.
Abstract in Cancer Research: Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice
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