| Autor: |
Karpov DS; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Demidova NA; N.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Gamaleya Str., 18, 123098 Moscow, Russia., Kulagin KA; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Shuvalova AI; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Kovalev MA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Simonov RA; N.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Gamaleya Str., 18, 123098 Moscow, Russia., Karpov VL; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Snezhkina AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Kudryavtseva AV; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str., 32, 119991 Moscow, Russia., Klimova RR; N.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Gamaleya Str., 18, 123098 Moscow, Russia., Kushch AA; N.F. Gamaleya National Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Gamaleya Str., 18, 123098 Moscow, Russia. |
| Abstrakt: |
Almost all people become infected with herpes viruses, including herpes simplex virus type 1 (HSV-1), during their lifetime. Typically, these viruses persist in a latent form that is resistant to all available antiviral medications. Under certain conditions, such as immunosuppression, the latent forms reactivate and cause disease. Moreover, strains of herpesviruses that are drug-resistant have rapidly emerged. Therefore, it is important to develop alternative methods capable of eradicating herpesvirus infections. One promising direction is the development of CRISPR/Cas systems for the therapy of herpesvirus infections. We aimed to design a CRISPR/Cas system for relatively effective long-term and safe control of HSV-1 infection. Here, we show that plasmids encoding the CRISPR/Cas9 system from Streptococcus pyogenes with a single sgRNA targeting the UL30 gene can completely suppress HSV-1 infection of the Vero cell line within 6 days and provide substantial protection within 9 days. For the first time, we show that CRISPR/CasX from Deltaproteobacteria with a single guide RNA against UL30 almost completely suppresses HSV-1 infection of the Vero cell line for 3 days and provides substantial protection for 6 days. We also found that the Cas9 protein without sgRNAs attenuates HSV-1 infection. Our results show that the developed CRISPR/Cas systems are promising therapeutic approaches to control HSV-1 infections. |
