Team:TP-CC San Diego

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Abstract

Cancer, a genetic disease resulting in uncontrollable cell growth, is mostly caused by somatic mutations acquired throughout an individual’s lifetime. Because it induces the increased expression of growth related genes, oncogene amplification is one of the driving forces of cancer cell replication. Recently, it was discovered that some oncogenes resided on extrachromosomal DNA (ecDNA). Like the DNA on chromosomes, ecDNAs are double stranded. A key difference, however, is the circular shape of ecDNAs; they are able to randomly distribute because they do not have centromeres, which increases heterogeneity in daughter cells. This can cause the cancerous tumors to develop faster resistance to current treatments. To target the ecDNA, we used CRISPR technology to create double strand breaks specifically in the ecDNA. Because ecDNA causes oncogene copy number to increase exponentially, utilizing CRISPR to create breaks in ecDNA decreases cancer cells’ replication speed.