A team of researchers in Australia have successfully used CRISPR-Cas9 to prevent the expression of a gene that drives cervical cancer. The researchers’ technique was shown to be effective at triggering cell death in cancer cells in mice.
Cervical cancer is the fourth most common cancer in women and accounts for around 6.6% of new cases. There are vaccines that provide protection against types of human papilloma virus known to cause cervical cancer and screening programs have helped to ensure women can receive treatment at a time when it is likely to be effective. However, in areas where women are not routinely screened and when cervical cancer is not detected until the latter stages, it is usually fatal. Early detection is key as the cancer has a high mortality rate.
CRISPR-Cas9 is a gene editing system used by prokaryotes to remove rogue sections of DNA from the genome that have been inserted by viruses. The system recognizes foreign DNA and cuts out the rogue section with an enzyme and rejoins the double stranded DNA. CRISPR-Cas9 has shown considerable promise in the lab as a highly specific gene editing tool, and studies have shown – with varying degrees of success – that the system can be used in humans to remove defective genes. After stringent testing in Europe and the United States the first clinical trials using CRISPR-Cas9 are now underway.
The Australian researchers turned to CRISPR-Cas9 to target genes in HPV-18 cervical cancer cells and used the system to insert new genetic material to prevent the rapid proliferation of cancer cells and the growth of tumors. The technique was used on mice that had been transplanted with HPV cancer cells. CRISPR-Cas9 was then used to prevent the expression of an HPV gene called E7, which drives cancer growth. The extra DNA inserted into the E7 gene causes it to be misread and prevented expression of a gene product required for cancer cell growth.
The researchers injected the mice with nanoparticles containing CRISPR-Cas9 8, 12, and 16 days after transplantation with the cancer cells. The treatment was shown to be effective at stopping growth of the tumors, but only temporarily. Mice that received 7 injections of the nanoparticles had their tumors eliminated and were cured.
This is one of the first in vivo CRISPR-Cas9 studies to be conducted that has proven to be effective at curing cancer. The study raises hopes that the treatment could one day be provided to women who have been diagnosed with cervical cancer. However, further studies are required to determine whether the treatment would be effective in humans and to ensure it is safe and there are no dangerous off-target edits made.
The study is detailed in the paper – Systemic Delivery of CRISPR/Cas9 Targeting HPV Oncogenes Is Effective at Eliminating Established Tumors – which was recently published in the journal Molecular Cell. DOI: 10.1016/j.ymthe.2019.08.012