Cargando…
CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9
Herpes simplex virus type 1 (HSV-1) is a leading cause of encephalitis and infectious blindness. The commonly used clinical therapeutic drugs are nucleoside analogues such as acyclovir. However, current drugs for HSV cannot eliminate the latent virus or viral reactivation. Therefore, the development...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302303/ https://www.ncbi.nlm.nih.gov/pubmed/37375504 http://dx.doi.org/10.3390/pathogens12060814 |
_version_ | 1785065015657627648 |
---|---|
author | Ying, Min Wang, Huadong Liu, Tongtan Han, Zengpeng Lin, Kunzhang Shi, Qing Zheng, Ning Ye, Tao Gong, Huinan Xu, Fuqiang |
author_facet | Ying, Min Wang, Huadong Liu, Tongtan Han, Zengpeng Lin, Kunzhang Shi, Qing Zheng, Ning Ye, Tao Gong, Huinan Xu, Fuqiang |
author_sort | Ying, Min |
collection | PubMed |
description | Herpes simplex virus type 1 (HSV-1) is a leading cause of encephalitis and infectious blindness. The commonly used clinical therapeutic drugs are nucleoside analogues such as acyclovir. However, current drugs for HSV cannot eliminate the latent virus or viral reactivation. Therefore, the development of new treatment strategies against latent HSV has become an urgent need. To comprehensively suppress the proliferation of HSV, we designed the CLEAR strategy (coordinated lifecycle elimination against viral replication). VP16, ICP27, ICP4, and gD—which are crucial genes that perform significant functions in different stages of the HSV infection lifecycle—were selected as targeting sites based on CRISPR-Cas9 editing system. In vitro and in vivo investigations revealed that genome editing by VP16, ICP27, ICP4 or gD single gene targeting could effectively inhibit HSV replication. Moreover, the combined administration method (termed “Cocktail”) showed superior effects compared to single gene editing, which resulted in the greatest decrease in viral proliferation. Lentivirus-delivered CRISPR-Cas9/gRNA editing could effectively block HSV replication. The CLEAR strategy may provide new insights into the potential treatment of refractory HSV-1-associated diseases, particularly when conventional approaches have encountered resistance. |
format | Online Article Text |
id | pubmed-10302303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103023032023-06-29 CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 Ying, Min Wang, Huadong Liu, Tongtan Han, Zengpeng Lin, Kunzhang Shi, Qing Zheng, Ning Ye, Tao Gong, Huinan Xu, Fuqiang Pathogens Article Herpes simplex virus type 1 (HSV-1) is a leading cause of encephalitis and infectious blindness. The commonly used clinical therapeutic drugs are nucleoside analogues such as acyclovir. However, current drugs for HSV cannot eliminate the latent virus or viral reactivation. Therefore, the development of new treatment strategies against latent HSV has become an urgent need. To comprehensively suppress the proliferation of HSV, we designed the CLEAR strategy (coordinated lifecycle elimination against viral replication). VP16, ICP27, ICP4, and gD—which are crucial genes that perform significant functions in different stages of the HSV infection lifecycle—were selected as targeting sites based on CRISPR-Cas9 editing system. In vitro and in vivo investigations revealed that genome editing by VP16, ICP27, ICP4 or gD single gene targeting could effectively inhibit HSV replication. Moreover, the combined administration method (termed “Cocktail”) showed superior effects compared to single gene editing, which resulted in the greatest decrease in viral proliferation. Lentivirus-delivered CRISPR-Cas9/gRNA editing could effectively block HSV replication. The CLEAR strategy may provide new insights into the potential treatment of refractory HSV-1-associated diseases, particularly when conventional approaches have encountered resistance. MDPI 2023-06-07 /pmc/articles/PMC10302303/ /pubmed/37375504 http://dx.doi.org/10.3390/pathogens12060814 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ying, Min Wang, Huadong Liu, Tongtan Han, Zengpeng Lin, Kunzhang Shi, Qing Zheng, Ning Ye, Tao Gong, Huinan Xu, Fuqiang CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title | CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title_full | CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title_fullStr | CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title_full_unstemmed | CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title_short | CLEAR Strategy Inhibited HSV Proliferation Using Viral Vectors Delivered CRISPR-Cas9 |
title_sort | clear strategy inhibited hsv proliferation using viral vectors delivered crispr-cas9 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10302303/ https://www.ncbi.nlm.nih.gov/pubmed/37375504 http://dx.doi.org/10.3390/pathogens12060814 |
work_keys_str_mv | AT yingmin clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT wanghuadong clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT liutongtan clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT hanzengpeng clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT linkunzhang clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT shiqing clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT zhengning clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT yetao clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT gonghuinan clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 AT xufuqiang clearstrategyinhibitedhsvproliferationusingviralvectorsdeliveredcrisprcas9 |