Gene editing platform could shape future application of CRISPR-based therapeutics

CRISPR gene editing

A team of researchers at Northwestern University in the US has devised a new platform for gene editing that could inform the future application of CRISPR-based therapeutics.

Using chemical design and synthesis, the team brought together the Nobel-prize winning technology with therapeutic technology born in their own lab to overcome a critical limitation of CRISPR. 

They created a system to deliver the cargo required for generating the gene editing machine known as CRISPR-Cas9. The team developed a way to transform the Cas-9 protein into a spherical nucleic acid (SNA) and load it with critical components to access a broad range of tissue and cell types. They also added the intracellular compartments required for gene editing.

Builds on a 25-year effort

The research ‘CRISPR Spherical Nucleic Acids,’ has been published in the Journal of the American Chemical Society. It shows how CRISPR SNAs can be delivered across the cell membrane and into the nucleus while also retaining bioactivity and gene editing capabilities.

It builds on a 25-year effort steered by nanotechnology pioneer Chad A Mirkin, who led the study, to uncover the properties of SNAs and the factors that distinguish them from their well-known linear cousin. 

Researchers are now evaluating SNAs as potent therapeutics in six human clinical trials, including ones for debilitating diseases like glioblastoma multiforme (brain cancer) and a variety of skin cancers.

“These novel nanostructures provide a path for researchers to broaden the scope of CRISPR utility by dramatically expanding the types of cells and tissues that the CRISPR machinery can be delivered to,” said Mirkin. 

“We already know SNAs provide privileged access to the skin, the brain, the eyes, the immune system, the GI track, heart and lungs. When this type of access is coupled to one of the most important innovations in biomedical science in the last quarter-century, good things will follow.” 

High gene editing efficiency

In this current research, Mirkin’s team used Cas9, a protein needed for gene editing, as the core of the structure, and attached DNA strands to its surface to make a new type of SNA. These SNAs effectively enter cells without the use of transfection agents and exhibit high gene editing efficiency between 32% and 47%.

The research team included graduate student researchers Chi Huang, Zhenyu (Henry) Han and Michael Evangelopoulos. The National Cancer Institute of the National Institutes of Health, the Sherman Fairchild Foundation, Dr John N Nicholson Fellowship, and the Alexander S Onassis Public Benefit Foundation supported the research.

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