For medical treatments to be most effective, they need to be localized exactly where they're needed, not roam free throughout the body and potentially cause other problems. Researchers at Rice University have developed a new way to activate treatments only in the right places, using an inert virus, magnetic nanoparticles and the gene-editing tool CRISPR-Cas9.
Emerging as a powerful potential tool in fighting everything from HIV to diabetes, CRISPR-Cas9 lets scientists make precise cut-and-paste edits to DNA to remove harmful genes and replace them with more beneficial ones. However, there are concerns that unintended mutations may be introduced elsewhere in the body, and although the issue is highly contentious, it's probably still safer to try to keep it local.
And that's what the Rice researchers set out to do. First, the CRISPR-Cas9 machinery is loaded into an inert virus to carry it safely through the body. While most scientists experimenting with CRISPR use what's known as adeno-associated viruses (AAV), the new study used a baculovirus vector (BV), which is based on a virus that infects certain moth species. The team says this choice was made because the BV can carry over 38,000 base pairs of DNA – up to eight times more than other methods.
Next, the team needed to make sure the CRISPR payloads are only released where they're needed. To do so, the team added an immune system protein called C3, which inactivates the BVs, as well as magnetic nanoparticles that override this when exposed to a magnetic field. In effect, that allows the team to inject the treatment, then focus a magnetic field on the area they want to treat.
"If we combine BV with magnetic nanoparticles, we can overcome this deactivation by applying the magnetic field," says Gang Bao, lead researcher on the study. "The beauty is that when we deliver it, gene editing occurs only at the tissue, or the part of the tissue, where we apply the magnetic field."
To test the treatment, the Rice team loaded the BVs with proteins from fireflies, which would glow under a microscope. That highlighted the fact that the payload was indeed being released exactly where it was supposed to be.
In that way, it sounds similar to other techniques scientists are using for targeted treatments. Ultrasound is a favorite trigger, and has been used in recent years to fight cancer by bursting heat-sensitive capsules, or pop sacs of pain relief medicine on demand. It's not the first time magnetic fields have been used in this way either, with previous studies putting the heat on tumors and helping to heal broken bones.
The new research was published in the journal Nature Biomedical Engineering.
Source: Rice University