Infantile hemangiomas (IHs) are common benign vascular tumors in childhood. Until recently, the role of miRNAs in the onset and progression of IH had never been investigated. Our scientists have recently shown a significant upregulation of the chromosome 19 miRNA cluster (C19MC) in IH specimens. Given the role of C19MC miRNAs in the regulation of cell proliferation, invasion, and differentiation, they hypothesize that temporal expression of C19MC plays a pivotal role in the onset of IH.
The C19MC miRNA is regulated by genomic imprinting with only the paternal allele expressed in the placenta. In addition, its expression is epigenetically regulated by DNA methylation of an upstream CpG rich promoter region. The inventors have developed novel assays that can measure the expression and/or CpG methylation of the upstream C19MC promoter region in post-natal tissue. In addition to this, they have also developed a novel method to treat IHs via a modified CRISPR/Cas 9 Synergistic Activation Mediator system which involves an upregulated actin gRNA (guide RNA) sequence that targets and inhibits the overexpressed C19MC promoter region commonly found in IHs. In summary, the inventors provide a novel method of measuring increased C19MC microRNA found in IHs and a new approach for designing novel, targeted miRNA-based therapeutics for the treatment of IH and other vascular malformations.
Proof of Concept for the CRISPR/Cas 9 System: Actin gRNA was Significantly Upregulated Compared to a Control