Gene therapies have the potential to treat neurodegenerative disorders such as Alzheimer’s and Parkinson’s, but they face a common barrier – the blood-brain barrier. Now, researchers at the University of Wisconsin-Madison have developed a way to transport therapeutics across the brain’s protective membrane to deliver brain-wide therapy with a combination of drugs and biological therapies.
“There is no cure yet for many of these devastating brain disorders,” says Shuqin “Sarah” Gong, MD, professor of ophthalmology, visual sciences, and biomedical engineering and researcher at the Wisconsin Discovery Institute. “Innovative brain-targeted delivery strategies may change this by enabling the non-invasive, safe and effective delivery of CRISPR genome editors that could in turn lead to genome-editing therapies for these diseases.”
CRISPR is a molecular toolkit for editing genes (for example, to correct mutations that might cause disease), but the toolkit is only useful if you can get to the job site through security. The blood-brain barrier is a membrane that selectively controls access to the brain, screening toxins and pathogens that may be present in the bloodstream. Unfortunately, the barrier prevents some useful therapies, such as some vaccines and gene therapy packages, from reaching their targets as they swarm with hostile invaders.
Injecting treatments directly into the brain is one way to get around the blood-brain barrier, but it is an invasive procedure that provides access to only nearby brain tissue.
“The promise of brain gene therapy and genome editing therapy rests on the safe and effective delivery of nucleic acids and genome editors to the whole brain,” says Gong.
In a study recently published in the journal Advanced materialsGong and members of her lab, including postdoctoral researcher and first author of the study Yuyuan Wang, describe a new family of silica nanocapsules that can deliver genome-editing tools to many organs around the body and then dissolve harmlessly.
By modifying the surfaces of silica nanocapsules with glucose and an amino acid fragment derived from the rabies virus, the researchers found that the nanocapsules can efficiently pass through the blood-brain barrier to achieve brain-wide gene editing in mice. In their study, the researchers demonstrated the ability of a CRISPR nanocapsule cargo to successfully modify genes in the brains of mice, such as one associated with Alzheimer’s disease called the amyloid protease gene.
Since the nanocapsules can be administered repeatedly intravenously, they can achieve higher therapeutic efficacy without the risk of topical and invasive methods.
The researchers plan to further improve the brain-targeting capabilities of the silica nanocapsules and evaluate their usefulness in treating various brain disorders. This unique technology is also being investigated for the delivery of biopharmaceuticals to the eyes, liver and lungs, which could lead to new gene therapies for other types of disorders.