27 August 2019

Scientists have used a new CRISPR gene editing method to improve immunotherapy, it has been announced.

The new method inactivates proteins which tumours uses to suppress the immune system, permitting cytotoxic T cells to attack lymphoma cells.

The research, led by Dr Mihue Jang and her team at the Korea Institute of Science and Technology, South Korea, in collaboration with scientists at Sejong University, appeared recently in the journal Biomaterials.

It involves CRISPR/Cas9 gene editing technology, which can remove or edit specific genes with high accuracy. Previous versions of the technology have been very successful in adherent cells, such as epithelial cells. However, the technique has not been as effective in floating ‘suspension’ cells, such as immune cells or blood cancer cells. The researchers say that this has slowed down progress in using the technology to combat blood cancers and immune diseases.

Dr Jang explains: “There are various kinds of genes that regulate immune activity, and technology for inducing safe and convenient immunotherapy is not yet sufficiently developed.”

To solve this problem, the team modified the Cas9 enzyme to add new functions. Specifically, the new Cas9 protein is more able to modify multiple genes simultaneously, and also penetrate into suspension cells without the need for artificial supplements.

Dr Jang and her colleagues used the modified CRISPR/Cas9 system to inactivate two proteins, PD-L1 and PD-L2, in a mouse lymphoma cell line. These proteins would normally attach to PD‑1 on T cells and block their anti-tumour activity. However, editing PD‑L1 and PD‑L2 in lymphoma cells removed this block, and so increased the ability of T cells to kill the lymphoma cells, both in the lab and in mice.

Dr Jang says: “This newly developed gene editing system can be applied to various types of immune cells and is thus expected to be used in the development of treatments for various diseases, including not only cancers but also autoimmune and inflammatory diseases.”

Source: Ju, A., Lee, S.W., Lee, Y.E., Han, K.C., Kim, J.C., Shin, S.C., Park, H.J., EunKyeong Kim, E., Hong, S., Jang, M. (2019) “A carrier-free multiplexed gene editing system applicable for suspension cells”,  Biomaterials, available from doi: 10.1016/j.biomaterials.2019.119298


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