Gene therapies have the potential to treat neurological disorders such as Alzheimer’s and Parkinson’s diseases, but they face a common barrier: the blood-brain barrier. Now, researchers at the University of Wisconsin-Madison have developed a way to move therapies across the brain’s protective membrane to deliver whole-brain therapy with a variety of drugs and biologic treatments.
“There is still no cure for many devastating brain disorders,” says Shaoqin “Sarah” Gong, a UW-Madison professor of ophthalmology and visual sciences and biomedical engineering and a researcher at the Wisconsin Discovery Institute. “Innovative brain-targeted delivery strategies may change that by enabling non-invasive, safe, and efficient 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 fix mutations that can cause disease), but the toolkit is only useful if it can get through workplace security. The blood-brain barrier is a membrane that selectively controls access to the brain, ruling out toxins and pathogens that may be present in the bloodstream. Unfortunately, the barrier prevents some beneficial treatments, such as certain vaccines and gene therapy packages, from reaching their targets because it groups them with hostile invaders.
Injecting treatments directly into the brain is one way to bypass the blood-brain barrier, but it is an invasive procedure that provides access only to nearby brain tissue.
“The promise of brain gene therapy and genome editing therapy rests on the safe and efficient delivery of nucleic acids and genome editors throughout the brain,” says Gong.
In a study recently published in the journal advanced materialsGong and members of his lab, including postdoctoral researcher and first author of the study Yuyuan Wang, describe a new family of nanoscale capsules made of silica that can deliver genome-editing tools to many organs in the body and then harmlessly dissolve. .
By modifying the surfaces of the silica nanocapsules with glucose and an amino acid fragment derived from the rabies virus, the researchers found that the nanocapsules could efficiently cross the blood-brain barrier to achieve whole-brain gene editing in mice. In their study, the researchers demonstrated the ability of the silica nanocapsule’s CRISPR payload to successfully edit genes in the brains of mice, such as one linked to Alzheimer’s disease called the amyloid precursor protein gene.
Because the nanocapsules can be administered repeatedly and intravenously, they can achieve greater therapeutic efficacy without risking more localized and invasive methods.
The researchers plan to further optimize the brain-targeting capabilities of the silica nanocapsules and test their utility for the treatment of various brain disorders. This unique technology is also being investigated for the delivery of biologics to the eyes, liver, and lungs, which may lead to new gene therapies for other types of disorders.