Nanoparticles Pass Muster as Vectors for Gene Therapy

Image: COURTESY OF THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

Gene therapy, in which a viral vector is used to modify defective genes or replace missing ones, has shown significant potential as a way of treating disease in animal models. But its use in humans has been hampered by safety concerns, including some fatalities in clinical trials. Researchers have thus been looking into the possibility of using nonviral vectors, which should carry fewer inherent risks, to deliver therapeutic genes. In a paper published online this week by the Proceedings of the National Academy of Sciences, scientists report that silicon nanoparticles can perform this task successfully in mice.
Paras N. Prasad of the State University of New York (SUNY) at Buffalo and his colleagues manufactured nanoparticles using organically modified silicon. The surface of these particles can be tailored to target specific cells. The team used the tiny units to transport a fluorescent marker gene to dopamine neurons in the brains of mice. After injecting the nanoparticles, the researchers observed brain cells fluorescing using a new imaging technique that works on live animals. According to the report, the study is the first in which a nonviral vector has shown efficacy comparable to that of a viral delivery system in an animal model. What is more, a month later none of the animals had experienced adverse effects from the procedure.

The researchers also investigated the possibility of manipulating the behavior of specific brain cells, instead of solely tagging their presence. In so doing, they discovered that the nanoparticles can be used to reactivate adult stem cells by altering a nuclear growth factor receptor. The team will next test the approach on larger animals. "In the future," says study co-author Earl J. Bergey, also at SUNY Buffalo, "this technology may make it possible to repair neurological damage caused by disease, trauma or stroke." --Sarah Graham