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Cell Presents Reptilian Model for Gene Editing, Melanoma Proteomics, More

A University of Georgia-led team has developed an approach that enables CRISPR-based editing of Anolis lizards, possibly paving the way for them to be used as a model for gene editing in reptiles. While CRISPR-Cas9 editing has pushed forward in mammals, fish, and amphibians, the researchers say it has lagged in reptiles due to difficulties in accessing reptilian zygotes. But as they report in Cell, the researchers found that the microinjection of CRISPR-Cas9 into unfertilized Anolis sagrei oocytes could produce targeted mutations. They say that this approach could likely be applied to other squamates.

Using a new mouse model of melanoma they devised, researchers from Weizmann Institute of Science and elsewhere examined the contribution of intra-tumor heterogeneity and tumor mutational burden to tumor aggressiveness and immune-mediated tumor rejection, as they report in Cell. To develop their experimental system, the researchers exposed a mouse melanoma cell line to UVB radiation, which increased its tumor mutational burden and aggressiveness, and then derived single-cell clones from that irradiated cell line. Through mixing and other analyses, they found that both number of clones making up a tumor and how diverse they are affects tumor aggressiveness. Additionally, they found that heterogeneity better predicts response to immunotherapy than tumor burden.

A Tel Aviv University-led team of researchers profiled the proteomes of melanoma samples from patients undergoing either advanced stage melanoma patients undergoing either tumor infiltrating lymphocyte (TIL)-based or anti-programmed death 1 (PD1) immunotherapy. As they report in Cell, the researchers quantified more than 10,000 proteins and found a role for lipid metabolism in increasing melanoma immunogenicity and boosting T cell-mediated killing. "Altogether, our proteomic analyses revealed association between the melanoma metabolic state and the response to immunotherapy, which can be the basis for future improvement of therapeutic response," the researchers write.