Pharmacy Researcher Develops Novel Approach to Treat Liver Diseases by Gene Editing

01/25/2017
Yizhou Dong
Yizhou Dong

Researchers from OSU and Tsinghua University, have a developed a new biotechnology platform, lipid-like nanoparticles (LLNs) in order to achieve effective and safe delivery of the CRISPR/Cas9 for gene editing. LLNs-mediated CRISPR/Cas9 delivery possesses the potential to treat a wide range of liver-related diseases.

The CRISPR/Cas9 system holds enormous promise for therapeutic applications. However, efficient and safe delivery of CRISPR/Cas9 is one of the key challenges for clinical uses. In order to address these issues, the team optimized lipid-like nanoparticals (LLNs), and effectively delivered Cas9 mRNA and single-guide RNA (sgRNA) to the liver, leading to in vivo targeting of Hepatitis B Virus (HBV) DNA and the proprotein convertase subtilisin/kexin type 9 (pcsk9) gene, a therapeutic target for treating hypercholesterolemia. HBV DNA is resistant to current therapies and is the main obstacle to a cure of Hepatitis B. While PCSK9 blocking antibody approved for treating hypercholesterolemia, more affordable and convenient therapies are still needed. CRISPR/Cas9 therapy, which permanently edits the target DNA, is high suitable for both of the targets.

“We are very excited about this collaborative and fruitful project together with the Tan lab at Tsinghua University. The results provide a proof-of concept of gene editing in mouse disease models using non-viral biomaterials, which offer promising genome-editing delivery tools for treating diverse diseases.” said senior author Yizhou Dong, who is an Assistant Professor in the Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, an Adjunct Professor in the Department of Biomedical Engineering, a member of the Center for Clinical and Translational Science, and a member of the Comprehensive Cancer Center at The Ohio State University.

Dong is one of the senior authors of a paper describing the findings in Cell Research. Xu Tan, an assistant professor at the Tsinghua University, is also a senior author. The paper’s lead authors include Chao Jiang, Miao Mei, Bin Li, and Xiurui Zhu in the lab of Dong and Tan, respectively. Other authors in the article include Wenhong Zu, Yujie Tian, Qiannan Wang, Yong Guo at Tsinghua University.