miRNA therapeutics by rAAVs

MicroRNAs (miRNA) are small RNA fragments that exert fundamental roles in cellular function and disease. One of our approaches is to develop a method that has the ability to inhibit miRNAs with a single injection of rAAV. This work promises to advance the field of miRNA functional genomics and miRNA therapeutics. We are also establishing a platform to investigate miRNA function by creating rAAV vectors that can increase or decrease miRNA abundance. We have created rAAV vectors for more than 40 mouse miRNAs. These vectors have been distributed to labs across the world and helping the research community accelerate their research. One example were we apply miRNA therapeutics is to regulate cholesterol metabolism, which is controlled by the most abundant miRNA in the liver, miR-122. One injection of our current vector reduces miR-122 by 80% in mouse liver and reduced their cholesterol levels by half. Another application is in collaboration with Dr. Weiqin Pan, where we demonstrated that a single injection of rAAV-mediated inhibition of miR-21 protects mice against lethal schistosome infection. Finally, we are investigating the role of miRNAs in the pathomechanism of hepatocellular carcinoma (HCC) and the development of new therapeutic strategies.