In a breakthrough, scientists at Northwestern University have developed new technology that improves gene editing efficiency, taking CRISPR-based gene editing techniques to the next level. Professor Chad Mirkin, a member of the NAS, directs this award winning team that has expertise spanning chemistry, engineering and medicine. Collectively, they created an innovative nanostructure that improves the delivery and function of CRISPR machinery inside cells by orders of magnitude.
Over the years, our group focused on clinically relevant lipid nanoparticles (LNPs) containing spherical nucleic acids (SNAs). These SNAs are extraordinary in their capacity to be detected and taken up by nearly every cell type. Recent results indicate that LNP-SNAs improve cell entry to a greater extent. They reduce toxicity markedly compared to existing, older delivery systems. This incredible new advance may lead to more targeted genetic alterations in humans and other applications such as gene therapies utilizing more focused human cures.
Innovations in Delivery Systems
The heart of this progress is the novel multiplexing of LNPs and SNAs. Mirkin’s team began with lipid nanoparticles (LNPs) designed to deliver the CRISPR machinery. Their aim was to enhance the delivery modes most commonly employed in gene editing. This new ability to incorporate SNAs into these lipid nanoparticles was a true game changer.
The little capsules are about 50 nanometers wide, small enough to slip in and out of cellular spaces with ease. The architecture of SNAs, which is highly specific to recognition by nearly all cell types, allows their easy uptake. In comparative laboratory tests, LNP-SNAs were able to enter cells with up to three times the efficiency of the best-in-class standard LNP delivery particles. That’s a big step in the advance of gene editing technology!
Additionally, the group noticed that cells preferentially absorbed these novel nanostructures, quickly internalizing them. This fast internalization is key to maximizing the collective efficiency of the broader gene editing R&D process. The researchers earned TCR an amazing, largely unprecedented victory. The CRISPR-Cas9 approach yielded an improvement in the success rate by more than 60% for targeted DNA repairs versus traditional methods, they reported.
Reduced Toxicity and Enhanced Efficiency
While the study points to real advances in efficacy of delivery, it focuses on the toxicity concerns. Conventional lipid particle delivery systems have resulted in serious adverse effects. The LNP-SNAs showed much lower toxicity while still producing strong delivery of CRISPR components.
This decrease in toxicity is especially important for therapeutic uses where safety is essential. These novel nanostructures reduce damaging side effects. Compared to the gene therapies available today, they provide a more exciting path for addressing genetic diseases while leaving patient health roots.
Additionally, the increased gene-editing efficiency—up to three times more effective than previous techniques—provides expanded opportunities for researchers and doctors. Mirkin’s team demonstrated that LNP-SNAs can be efficiently introduced in a range of cellular cultures. Among them are skin cells, white blood cells, human bone marrow stem cells, and human kidney cells. This versatility is a testament to the far-reaching applicability of this technology, including in the fields of regenerative medicine and cancer immunotherapy.
The Future of Gene Editing
Chad Mirkin is the George B. Rathmann Professor of Chemistry, Institute for Nanotechnology, and the Director of the International Institute for Nanotechnology at Northwestern University. He is a professor of chemical and biological engineering, biomedical engineering, and materials science and engineering at the McCormick School of Engineering. He’s been a dynamo in reshaping the active transportation scene in medicine at Northwestern’s Feinberg School of Medicine. Further, he is the founding executive director of Northwestern’s International Institute for Nanotechnology.
Mirkin’s role in so many different disciplines puts him at the forefront of the interdisciplinary research efforts geared toward the rapid advancement of medical technology. His leadership with LNP-SNAs exemplifies his commitment to innovation. It goes a long way toward helping the scientific community understand the process of gene editing itself.
These impacts of this research are not confined to the classroom. There are significant exciting opportunities for practical application to fields such as medicine and biotechnology. Scientists are already testing the opportunities that LNP-SNAs might offer for CRISPR gene editing. Their efforts might lead to new therapies for currently untreatable genetic diseases.