ETH enables new approaches to cancer therapies with stealth gene scissors

(CONNECT) The research group of Nicola Aceto, Professor of Molecular Oncology at ETH Zurich, has put a cloak of invisibility on the Crispr/Cas9 technology, also known as gene scissors, according to a report by the university. The motivation for making them "invisible" to the immune system of mice was that the gene scissors consist primarily of bacteria, which leads to problems in the mouse model: the animals' immune system reacts to these bacteria. But this makes Crispr screens unreliable.

In such screens, hundreds of tumor cells are quickly produced, each with a different gene switched off. Transplanted into mice, it then becomes apparent which of the silenced genes influences the development and spread of cancer. However, if their immune system were to react, the respective effect would no longer be reliably recognizable.

The ETH team has now demonstrated this in detail for the first time in its study. It also developed an alternative method for Crispr/Cas9 screens that triggers virtually no immune reaction. The tumor cells only come into temporary contact with the gene scissors for this camouflage cap. In addition, only tumor cells in which a gene has been successfully silenced are isolated. In addition, the researchers replaced the so-called reporter genes with another gene whose product differs only minimally from an endogenous protein in the mice.

The group has already discovered a new target for breast cancer therapy: silencing two genes called AMH and AMHR2 drastically reduced the number of metastases in a mouse model of breast cancer. Further investigations of the data from patients revealed that a high level of AMH protein in the tumor is indeed associated with more relapses and greater mortality. "With Crispr in stealth mode," says Professor Aceto, "we can now uncover connections that were previously hidden." ce/mm