Gene Editing for the Elimination of Herpes Simplex Virus and Other Persistent Viral Infections
Keith Jerome, MD, PhD
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
Persistent viruses, such as herpes simplex (HSV), hepatitis B (HBV), and Human immunodeficiency virus (HIV) remain serious causes of human suffering and death. After initial infection, these viruses establish latency or stable persistence in long-lived cells. Current antivirals can suppress viral replication, but they do not eliminate the persistent viral forms, which serve as the source for viral reactivation once treatment is stopped. To address the need for novel therapeutic approaches to cure these infections, we have evaluated the use of gene-editing endonucleases to directly target persistent virus in vivo. For HSV, we have demonstrated that specific serotypes of AAV can efficiently deliver anti-HSV meganucleases to the trigeminal (TG) and superior cervical (SCG) ganglia of mice with latent infection, resulting in a reduction in ganglionic HSV of more than 90%. For HBV, we have observed that AAV-delivered anti-HBV CRISPR/Cas9 leads to dramatic improvement in human hepatocyte survival in a humanized mouse model, along with an apparent reduction in HBV cccDNA. For HIV, the use of gene editing in vivo remains challenging due to the distributed nature of the reservoir, and thus new and innovative delivery approaches are key. Taken together, our results support continued efforts toward gene editing as an antiviral strategy, emphasize the importance of efficient delivery for in vivo gene editing applications, and should encourage workers in the field to appreciate the full diversity of available gene-editing nucleases.
The International Society for Antiviral Research (ISAR) is an internationally recognized organization for scientists involved in basic, applied, and clinical aspects of antiviral research. The Society main event is the annual International Conference on Antiviral Research (ICAR), a truly interdisciplinary meeting which attracts the interest of chemists, biologists, and clinicians.