Healthcare (Commonwealth Union) – The gene editing tool CRISPR has the potential to redefine medicine by rewriting the genetic instructions associated with various diseases according to researchers. However, they indicated that this potential remains largely underutilized until scientists can transfer its gene-editing components safely and efficiently to the appropriate cells and tissues.
Chemists presently at Northwestern University have produced a novel type of nanostructure that significantly improves CRISPR delivery and may expand its applications.
The lipid nanoparticle spherical nucleic acids (LNP-SNAs), is a minuscule structure that can carry all the essential CRISPR tools — Cas9 enzymes, guide RNA, as well as a DNA repair template — encapsulated inside a dense, sheilded DNA shell. This coating does not just protect the cargo but also directs the nanoparticles to specific organs and tissues, while permitting simpler entry into cells.
The laboratory research carried out across multiple human and animal cell types demonstrated that LNP-SNAs penetrated cells up to three times more effectively than conventional lipid particles utilised in COVID-19 vaccines, produced considerably less toxicity, and tripled gene-editing efficiency. Moreover, they elevated the accuracy of DNA repairs by more than 60% when contrasted with current techniques.
The findings were published in the Proceedings of the National Academy of Sciences.
This research marks a major step toward safer and more dependable genetic therapies, highlighting how a nanomaterial’s structural design — not just its components — can determine its effectiveness. This concept forms the foundation of structural nanomedicine, a growing field pioneered by Northwestern’s Chad A. Mirkin and his team, now pursued by hundreds of scientists worldwide.
“CRISPR is an incredibly powerful tool that could correct defects in genes to decrease susceptibility to disease and even eliminate disease itself,” explained Mirkin, who was the lead of the new study. “But it’s difficult to get CRISPR into the cells and tissues that matter. Reaching and entering the right cells — and the right places within those cells — requires a minor miracle. By using SNAs to deliver the machinery required for gene editing, we aimed to maximize CRISPR’s efficiency and expand the number of cell and tissue types that we can deliver it to.”
A trailblazer in nanotechnology and nanomedicine, Mirkin holds the George B. Rathmann Professorship of Chemistry at Northwestern University’s Weinberg College of Arts and Sciences. He also serves as a professor of chemical and biological engineering, biomedical engineering, and materials science and engineering at the McCormick School of Engineering, a professor of medicine at the Feinberg School of Medicine, executive director of the International Institute for Nanotechnology, and is affiliated with the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.
Once CRISPR machinery reaches its intended location inside a cell, it can turn genes off, correct mutations, introduce new functions, and more. However, CRISPR cannot enter cells on its own—it always requires a carrier.
At present, researchers typically rely on viral vectors or lipid nanoparticles (LNPs) for delivery. Viruses, naturally adept at infiltrating cells, are highly effective but can trigger immune reactions in the body, which may lead to uncomfortable or even dangerous side effects. LNPs are generally safer but less efficient, often becoming trapped in cellular compartments called endosomes, where they cannot release their genetic cargo.
Mirkin indicated that just a small portion of the CRISPR machinery successfully enters the cell, and an even tinier fraction reaches the nucleus. He further pointed out that another approach involves taking cells out of the body, delivering the CRISPR components, and then returning the cells to which he started points out how, this method is highly inefficient and hardly practical.
To tackle this challenge, Mirkin’s team turned to spherical nucleic acids (SNAs) — DNA and RNA arranged in a globular, rather than linear, structure — first developed in Mirkin’s Northwestern lab. These spherical genetic constructs encase a nanoparticle core, which can be loaded with therapeutic cargo. Measuring about 50 nanometers across, the tiny particles are known for their ability to enter cells efficiently and deliver their payloads with precision.
The role of SNAs was highlighted in the study, which may be further evaluated by various life science researchers.
