An important gap in developing new cancer treatments has been the development of safe and efficient delivery systems for getting drugs into cancer cells once they are in our bodies. Researchers at Tel Aviv University have recently developed a new CRISPR-based genome editing therapy using a cutting-edge delivery system. Their research uses the CRISPR technology, where a special kind of protein called an enzyme cuts specific DNA sequences to introduce mutations. Because the large size of this enzyme makes it hard to enter cancer cells, current research into CRISPR cancer treatments have shown low efficiency.

To address this issue, the researchers designed a delivery system where the RNA molecule responsible for creating the enzyme is encapsulated by a layer of long fatty molecules called lipids, allowing them to be easily taken up by cancer cells. They further engineered the lipid particles to target cancer cells specifically by binding to certain proteins that are present on the outside of cancer cells. Once inside the cancer cells, the enzyme that is produced cuts the DNA of a gene required for cell growth, leading to the death of the cell. The researchers chose to tackle two very aggressive and difficult-to-treat cancers, glioblastoma and metastatic ovarian cancer. When studying these two deadly cancers in mice, they observed up to 80% gene editing of the tumor cells, significant inhibition of tumor growth, and up to an 80% increase in overall survival. There were no signs of toxicity or of an adverse immune response against the therapy.

These studies present the highest survival improvement to date in these two aggressive tumors after a single treatment. While more extensive evaluation of toxicity is needed before clinical development, this delivery system with high efficiency editing presents an exciting opportunity for broad clinical translation. Interestingly, this lipid delivery system is similar to those currently being used in the mRNA vaccines being developed for COVID-19. This strategy could also be extended to edit other tumor-dependent genes, tumor-specific oncogene mutations, or even used for gene editing therapy of other genetic diseases.

Professor Dan Peer is VP for R&D and Head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University. The research was conducted by Dr. Daniel Rosenblum together with Ph.D. student Anna Gutkin and colleagues in Prof. Peer’s laboratory.

Managing Correspondent: Lauren Davancaze

Press Articles: “Revolutionary CRISPR-based genome editing system treatment destroys cancer cells,” Medical Xpress

Original Journal Article: “CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy,” Science Advances