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Guocai Zhong, PhD

Assistant Professor, RNA Therapeutics Institute, Gene Therapy Center

Research Focus - RNA switches and Regulatable gene therapies

Our lab is mainly focused on RNA switch engineering and regulatable gene therapy development. Adeno-associated virus (AAV) vector-mediated in vivo somatic cell gene therapies, such as gene-replacement, gene-addition, or genome-editing therapies, have shown great therapeutic potential for treating a wide range of human diseases. However, safer and broader applications of AAV gene therapy are in part limited by the lack of useful molecular tools for precise control of therapeutic transgene expression.  RNA switches, structured small noncoding RNA domains that control gene expression independent of any protein factors, represent a class of very promising tools for transgene regulation. A body of our prior studies have moved artificial RNA switches from working efficiently in vitro to now functioning with wide dynamic ranges in animals. These studies also established a strong proof of concept that RNA switches could expand the use AAV gene therapies to broader disease indications.

We are now very interested in the following three directions:

  1. Tool development: engineering parts (novel RNA switches, other RNA-based tools, and therapeutic payloads) for the development of AAV- or mRNA-based in vivo gene therapies.
  2. Mechanism studies: tracking the intracellular trafficking of RNA switch-containing mRNAs and investigating how the in-house developed RNA switches work in mammalian cells.
  3. Gene therapy applications: developing RNA switch-regulated tunable and/or terminable AAV gene-addition/gene-editing therapies or mRNA-based therapies for fatal genetic diseases, metabolic disorders, and infectious diseases.

We are always interested in possible collaborations with researchers who focus on the biology of specific diseases or novel therapeutic targets where our regulatable gene therapy technology might be applied.

Representative Publications

  • A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo. Guocai Zhong, Haimin Wang, Wenhui He, Yujun Li, Huihui Mou, Zachary J. Tickner, Mai H. Tran, Tianling Ou, Yiming Yin, Huitian Diao & Michael Farzan. Nature Biotechnology volume 38, pages169–175 (2020) Read Publication