Gene therapies have the potential to treat neurological diseases like 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 method to move therapies across the brain’s protective membrane to enable brain-wide therapy with a range of biologic drugs and treatments.
“Many devastating brain diseases still have no cure,” said Shaoqin “Sarah” Gong, UW-Madison professor of ophthalmology and visual sciences and biomedical engineering and a researcher at the Wisconsin Institute for Discovery. “Innovative brain-targeted delivery strategies could change this by enabling non-invasive, safe, and efficient delivery of CRISPR genome editors, which in turn could lead to genome-editing therapies for these diseases.”
CRISPR is a molecular toolkit for editing genes (e.g. to correct mutations that can cause disease), but the toolkit is only useful if it can get through security to the scene. The blood-brain barrier is a membrane that selectively controls access to the brain and filters out toxins and pathogens that may be present in the bloodstream. Unfortunately, the barrier prevents some useful treatments, like certain vaccines and gene therapy packages, from reaching their targets because they coincide with enemy invaders.
Injecting treatments directly into the brain is one way to bypass the blood-brain barrier, but it’s an invasive procedure that only provides access to nearby brain tissue.
“The promise of brain gene therapy and genome editing therapy lies in the safe and efficient delivery of nucleic acids and genome editors to the entire brain,” says Gong.
In a study recently published in the journal Advanced MaterialsGong and her lab members, including postdoctoral researcher and study lead author Yuyuan Wang, describe a new family of nanoscale silica capsules that can transport genome-editing tools to many organs in the body and then harmlessly disintegrate.
By modifying the surfaces of the silica nanocapsules with glucose and a rabies virus-derived amino acid fragment, the researchers found that the nanocapsules could efficiently cross the blood-brain barrier to achieve brain-wide gene editing in mice. In their study, the researchers demonstrated the ability of the CRISPR charge of the silica nanocapsule to successfully edit genes in the mouse brain, such as a gene 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 abilities of the silica nanocapsules and evaluate their usefulness for treating various brain diseases. This unique technology is also being studied for the delivery of biologics to the eyes, liver and lungs, which may lead to new gene therapies for other types of diseases.