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Mast cells regulate the immune response
"Current treatments for mast cell carcinoma target the receptor signal encoded by the c-KIT gene, and c-KIT mutations associated with disease development may have a negative impact on the efficacy of current treatments," North Carolina State University Immunology Said Glenn Cruse, assistant professor and corresponding author of the study
Cruse and a team of researchers from North Carolina State University and the National Institutes of Health (NIH) used a technique called exon skipping to generate frameshift mutations
Before the gene or protein is produced, the pre-mRNA consisting of coding and non-coding regions (called exons and introns) is spliced, so the introns are removed, and only the exons—the gene’s " Production order"-retained
Researchers use this mechanism to bind a short RNA molecule called an oligonucleotide to exon 4 in the pre-mRNA of c-KIT, effectively tricking the splicing protein into thinking that the exon is an intron And remove it
Cruse said: "We are changing the information that makes proteins-switch the'on' switch to'off'
The researchers used the frameshift c-KIT mRNA method on mast cell leukemia cells in vitro and found that KIT protein expression, signal transduction and function were reduced
"Another advantage of our technology is that it solves the problem of evading degradation," Cruse said
This research was published in the journal Molecular Therapy and was supported by the National Institutes of Health
Douglas B.