Gene therapies have the potential to treat neurological disorders like Alzheimer’s and Parkinson’s diseases, but they face a common barrier - the blood-brain barrier.
Researchers at the University of Wisconsin–Madison have developed a way to move therapies across the blood-brain barrier to deliver brain-wide therapy with a range of biological medications and treatments.
"There is no cure yet for many devastating brain disorders," says Shaoqin "Sarah" Gong, UW–Madison professor of ophthalmology and visual sciences and biomedical engineering and researcher at the Wisconsin Institute for Discovery. "Innovative brain-targeted delivery strategies may change that by enabling noninvasive, safe, and efficient delivery of CRISPR genome editors that, in turn, could lead to genome-editing therapies for these diseases."
CRISPR is a molecular toolkit for editing genes (for example, it is used to correct mutations that may cause disease), but the toolkit is only useful if it can get through security to the required site. The blood-brain barrier selectively controls access to the brain, screening out toxins and pathogens that may be present in the bloodstream. Unfortunately, because of the barrier, some of the beneficial treatments, like certain vaccines and gene therapy, are not possible, as it prevents them from reaching their target.
Injecting treatments directly into the brain is one way to pass through the blood-brain barrier, but this is an invasive procedure that provides access only to nearby brain tissue.
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 pass through the blood-brain barrier to achieve brain-wide gene editing in mice.
In their study, they demonstrated the capability of the silica nanocapsule’s CRISPR cargo to successfully edit genes in the brains of mice, such as one related to Alzheimer’s disease called the amyloid precursor protein gene. Because the nanocapsules can be administered repeatedly and intravenously, they can achieve higher therapeutic efficacy without risking more localized and invasive methods.
The researchers are planning to optimize the silica nanocapsules’ brain-targeting capabilities and evaluate their usefulness for the treatment of various brain disorders.
This technology is also being investigated for the delivery of biologics to the eyes, liver, and lungs, which can lead to new gene therapies for other types of disorders.
Reference:
Yuyuan Wang, Xiuxiu Wang, Ruosen Xie, Jacobus C. Burger, Yao Tong, Shaoqin Gong, 29 November 2022, Overcoming the Blood–Brain Barrier for Gene Therapy via Systemic Administration of GSH-Responsive Silica Nanocapsules.
By Abhishek Muthuraj
Comments