overview: Researchers have developed a new family of nanoscale capsules that can deliver CRISPR gene-editing tools to various organs of the body before harmlessly dissolving. The capsule entered the mouse brain and successfully edited a gene associated with Alzheimer’s disease.
sauce: University of Wisconsin-Madison
Gene therapy has the potential to treat neurological disorders such as Alzheimer’s disease and Parkinson’s disease, but faces a common barrier: the blood-brain barrier.
Researchers at the University of Wisconsin-Madison are now developing ways to transcend the brain’s protective membranes to deliver treatments throughout the brain using a variety of biologic medications and treatments.
“There are still no cures for many of the devastating brain disorders,” says Shaoqin “Sarah” Gong, professor of ophthalmology and vision sciences and biomedical engineering at UW-Madison and researcher at the Wisconsin Institute for Discovery. says.
“Innovative brain-targeted delivery strategies may lead to genome-editing therapies for these diseases by enabling non-invasive, safe and efficient delivery of CRISPR genome editors.”
CRISPR is a molecular toolkit for editing genes (e.g., to correct mutations that can cause disease), but this toolkit is only useful if it can get through security and into the field. increase.
The blood-brain barrier is a membrane that selectively controls access to the brain and excludes toxins and pathogens that may be present in the bloodstream. Unfortunately, this barrier prevents beneficial therapies such as certain vaccines and gene therapy packages from reaching their targets.
Injecting therapeutics directly into the brain is one way to bypass the blood-brain barrier, but it is an invasive procedure that only provides access to nearby brain tissue.
“The feasibility of brain gene therapy and genome editing therapies relies on the safe and efficient delivery of nucleic acids and genome editors throughout the brain,” says Gong.
A study recently published in the journal advanced materialsGong and members of her lab, including Yuyuan Wang, a postdoctoral researcher and lead author of the study, carried genome-editing tools to many organs around the body and then dissolved them harmlessly, made of silica. A new family of nanoscale capsules is described.
By modifying the surface of silica nanocapsules with glucose and rabies virus-derived amino acid fragments, the researchers found that the nanocapsules could efficiently cross the blood-brain barrier to achieve gene editing throughout the mouse brain. bottom.
In their study, researchers demonstrated the ability of CRISPR cargoes in silica nanocapsules to successfully edit genes in the mouse brain, including one associated with Alzheimer’s disease called the amyloid precursor protein gene.
Nanocapsules can be administered intravenously repeatedly, thus achieving greater therapeutic efficacy without compromising more local and invasive methods.
The researchers plan to further optimize the brain-targeting ability of silica nanocapsules and evaluate their utility for treating various brain disorders. This unique technology is also being investigated for delivery of biologics to the eye, liver and lungs, and may lead to new gene therapies for other types of diseases.
About this nanotech and CRISPR research news
author: Kaitlyn Henning
sauce: University of Wisconsin-Madison
contact: Caitlin Henning – University of Wisconsin-Madison
image: image is public domain
Original research: closed access.
“Overcoming the Blood-Brain Barrier for Gene Therapy by Systemic Administration of GSH-Responsive Silica Nanocapsules” by Shaoqin “Sarah” Gong et al. advanced materials
Overcoming the blood-brain barrier for gene therapy by systemic administration of GSH-responsive silica nanocapsules
CRISPR genome editing has the potential to treat the underlying causes of many genetic diseases, including central nervous system (CNS) disorders. However, the potential for brain-targeted therapeutic genome editing relies on efficient delivery of biologics to bypass the blood-brain barrier (BBB), which poses a major challenge in the development of CRISPR therapeutics. I’m here.
A library of glutathione (GSH)-responsive silica nanocapsules (SNCs) was generated and screened for the delivery of brain-targeted biologics via systemic administration.
In vivo studies have shown that systemically delivered SNC coupled with glucose and rabies virus glycoprotein peptides under glycemic control can efficiently bypass the intact BBB, transfecting different genes in both Ai14 reporter mice and wild-type. It enables the whole-brain delivery of various biologics, including the CRISPR genome editor targeting mice.
Notably, systemic delivery of Cre mRNA in Ai14 mice resulted in up to 28% neuronal editing, up to 6.1% amyloid precursor protein (app) gene editing (19.1% reduction in expression levels of intact APP), and up to 3.9% tyrosine hydroxylase (Eye) gene editing in wild-type mice (resulting in a 30.3% reduction in the expression level of TH) is observed.
This versatile SNC nanoplatform may provide novel strategies for the treatment of central nervous system diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases.