Anti-Sense DNA: Nanotechnology and Gene Therapy for Cancer
By attaching strands of "antisense" DNA to nanometer-scale particles made of gold, scientists at Northwestern University have significantly enhanced the strands' ability to suppress the production of dangerous proteins--such as those that cause cancer.
The Northwestern team, led by Chad A. Mirkin, director of the university's Center for Cancer Nanotechnology Excellence, was supported in part by the National Science Foundation. The center itself is funded by the national Cancer Institute. The team's findings are detailed in the May 19 issue of the journal Science.
A Eurekalert newsrelease provides further helpful details:
When compared to antisense DNA complexed with commercial agents such as Lipofectamine and Cytofectin, the antisense nanoparticles were more effective in gene knockdown (decreasing gene expression and protein production), were less susceptible to degradation resulting in longer lifetimes, exhibited lower toxicity and were more readily absorbed by cells, exhibiting a greater than 99 percent uptake.
"When mutations in the body's genetic material cause too many copies of certain proteins, cancer and other diseases can result," said Chad A. Mirkin, director of Northwestern's Center for Cancer Nanotechnology Excellence, who led the study. "Whereas typical drugs target the proteins, it is possible through gene therapy to target the genetic material itself before it is ever made into copies of harmful proteins. One way to target the genetic material is to block the messenger RNA by using 'antisense DNA,' which prevents the message from ever becoming a protein."
Once inside cells, the DNA-modified nanoparticles act as messenger RNA "sponges" that bind to their targets and prevent them from being converted into proteins.
In their experiments the researchers targeted mRNA sequences that code for enhanced green fluorescent protein (EGFP) expressed in a mouse cell. The antisense sequence of the DNA attached to the nanoparticles was complementary to the mRNA for EGFP expression. When the nanoparticles were introduced to the cells the fluorescence dimmed -- a result of the nanoparticles binding to the mRNA and shutting down the protein's expression, or fluorescence.
"In the future, this exciting new class of antisense material could be used for the treatment of cancer and other diseases that have a genetic basis," said Mirkin, who is George B. Rathmann Professor of Chemistry, professor of medicine and professor of materials science and engineering.
There are many steps in the pathway from gene to protein to final product/effect, where gene therapies of different types can be utilised. The combination of genetic therapies with nanotechnology will be a particularly potent approach in the near future, for combatting cancer and other diseases involving faulty genes.