Researchers at Tel Aviv University (TAU) have demonstrated the CRISPR-Cas9 gene editing tool is effective at treating metastatic cancers in vivo.
CRISPR is already being used by researchers to make precise edits to the DNA to correct harmful mutations and several clinical trials currently underway; however, efforts to harness CRISPR for use in cancer treatments have stumbled due to the low editing efficiency in tumors. The delivery system normally used to get the CRISPR system into cells – Adeno-Associated Viruses AAVs – is not without problems and potentially can be toxic.
To get around these problems, the researchers developed a new type of delivery system for specifically targeting cancer cells. The system is based on lipid nanoparticles (LNPs) which deliver a messenger RNA which encodes for the Cas9 enzyme, which makes the cut to the DNA in the cancer cells and kills them.
The researchers tested their new system on two of the deadliest forms of cancer: Glioblastoma – a form of cancer affecting the brain and spinal cord – and metastatic ovarian cancer. Both of these forms of cancer are highly aggressive. Glioblastoma accounts for around 16% of primary brain tumors and is almost always fatal, with a five-year survival rate of just 3%. Metastatic ovarian cancer similarly has a very high mortality rate, with only a third of patients surviving.
The researchers used their CRISPR system and new delivery method to target the cancer cells in mice and report that the survival rate was almost doubled after a single round of treatment. They achieved around 70% of gene editing in vivo in mice with aggressive orthotopic glioblastoma, which reduced tumor growth by 50% and improved the survival rate by 30%. The researchers also engineered their CRISPR LNPs for antibody-targeted delivery for treating disseminated ovarian tumors and saw editing of around 80% which inhibited tumor growth and increased survival by 80%.
“This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal,” said Professor Dan Peer, co-author of the paper. Peer also explained that in contrast to chemotherapy, after the DNA of a cancer cell has been altered using CRISPR, there is no way that the cell will recover and become active again. There are also no known side effects from the CRISPR treatment, in contrast to chemotherapy.
The researchers now plan to conduct experiments on blood cancers and genetic diseases such as Duchenne muscular dystrophy.
You can read more about the study in the paper – CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy – which was recently published in the journal Science Advances. DOI: 10.1126/sciadv.abc9450