DNA Delivery in Gene Therapy

Gene therapy is the hope of the future, but scientists still haven’t overcome the obstacles encountered while delivering DNA into the nuclei of living cells actively doing their job in the human body. Thus far, it has been a challenge trying to get foreign genes to continue functioning for the same amount of time and at the same level as native genes.

One summer at the NIH, my project was to find a way to transfect (deliver DNA into) malaria parasites. Our chosen method was to electrocute the parasites with a high voltage current and hope they’d open up the pores in their cell membrane allowing the DNA to float in and do its job (aka electroporation). It was fun to see the arcs of electricity jump between the sample and the machines eliciting sissy shrieks from me. Electroporation wouldn’t work on any higher level organisms, though.

Other methods that have been tried before in therapeutic gene delivery is the use of adenovirus and retrovirus vectors, but their use is risky and impractical. Recently, silicon-based nanoparticles have been successfully used to deliver genes into the brains of living mice. (BioScience Technology, July 25, 2005)

Using amino-functionalized organically modified silica (ORMOSIL) nanoparticles coated with amino groups that bind with DNA, scientists targeted dopamine neurons that degenerate in Parkinson’s disease. The DNA was able to traverse the cell membrane and successfully function by expressing a fluorescent marker gene. Most encouraging, the mice did not appear to suffer from any side-effects four weeks after transfection and the results appeared to equal or surpass those from viral vector experiments.

We also succeeded in transfecting Plasmodium falciparum malaria parasites that summer which gave scientists another tool for genetic analysis. Electrocution as a method of gene therapy certainly won’t work in humans, but injecting nanoparticles into the brain doesn’t sound very pleasant either. Nevertheless, gene therapy to repair neurological damage caused by stroke, Parkinson’s and Alzheimer’s disease will hopefully be more effective than current treatment.