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CRISPR Enzyme ThermoCas9 Selectively Cuts Tumor DNA Using a Methylation 'Address'

The finding points to a way to aim gene editing at cancer cells with less risk to healthy tissue.

Overview

  • Researchers from Wageningen University and Van Andel Institute report in Nature that ThermoCas9 cut DNA in human tumor cell lines while leaving healthy cells untouched.
  • ThermoCas9 reads DNA methylation, a small chemical tag that controls gene activity, and uses differences between cancer and healthy cells to guide where it cuts.
  • Structural analyses show the enzyme recognizes a DNA motif next to its target that overlaps a common human methylation site, which explains its selectivity.
  • Experiments in cultured breast and colorectal cancer cells confirmed selective cutting, yet the study did not demonstrate that this damage killed tumor cells.
  • The teams say next steps include increasing DNA damage to test for tumor cell death and probing uses in other diseases marked by abnormal methylation.