Microglia-Specific Promoter Activities of HEXB Gene
Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expres...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.808598/full |
| _version_ | 1819104669691019264 |
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| author | Sahil Shah Sahil Shah Lilly M. Wong Kendra Ellis Kendra Ellis Brittany Bodnar Brittany Bodnar Sami Saribas Sami Saribas Julia Ting Julia Ting Zhengyu Wei Zhengyu Wei Yuyang Tang Xianwei Wang Hong Wang Binhua Ling David M. Margolis David M. Margolis J. Victor Garcia Wenhui Hu Wenhui Hu Guochun Jiang Guochun Jiang |
| author_facet | Sahil Shah Sahil Shah Lilly M. Wong Kendra Ellis Kendra Ellis Brittany Bodnar Brittany Bodnar Sami Saribas Sami Saribas Julia Ting Julia Ting Zhengyu Wei Zhengyu Wei Yuyang Tang Xianwei Wang Hong Wang Binhua Ling David M. Margolis David M. Margolis J. Victor Garcia Wenhui Hu Wenhui Hu Guochun Jiang Guochun Jiang |
| author_sort | Sahil Shah |
| collection | DOAJ |
| description | Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at −135, −134, and −170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS. |
| first_indexed | 2024-12-22T02:10:02Z |
| format | Article |
| id | doaj.art-54a2bdcd07e54840b12bb705d5db3997 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T02:10:02Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-54a2bdcd07e54840b12bb705d5db39972022-12-21T18:42:26ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-03-011610.3389/fncel.2022.808598808598Microglia-Specific Promoter Activities of HEXB GeneSahil Shah0Sahil Shah1Lilly M. Wong2Kendra Ellis3Kendra Ellis4Brittany Bodnar5Brittany Bodnar6Sami Saribas7Sami Saribas8Julia Ting9Julia Ting10Zhengyu Wei11Zhengyu Wei12Yuyang Tang13Xianwei Wang14Hong Wang15Binhua Ling16David M. Margolis17David M. Margolis18J. Victor Garcia19Wenhui Hu20Wenhui Hu21Guochun Jiang22Guochun Jiang23Center for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesUniversity of North Carolina HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesUniversity of North Carolina HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesSouthwest National Primate Research Center, Host-Pathogen Interaction Program, Texas Biomedical Research Institute, San Antonio, TX, United StatesUniversity of North Carolina HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Medicine, Microbiology and Immunology, Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesInternational Center for the Advancement of Translational Science, Division of Infectious Diseases, UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesCenter for Metabolic Disease Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesUniversity of North Carolina HIV Cure Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesAdeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at −135, −134, and −170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS.https://www.frontiersin.org/articles/10.3389/fncel.2022.808598/fullHexBCD68microgliaastrocytesgene therapygene editing |
| spellingShingle | Sahil Shah Sahil Shah Lilly M. Wong Kendra Ellis Kendra Ellis Brittany Bodnar Brittany Bodnar Sami Saribas Sami Saribas Julia Ting Julia Ting Zhengyu Wei Zhengyu Wei Yuyang Tang Xianwei Wang Hong Wang Binhua Ling David M. Margolis David M. Margolis J. Victor Garcia Wenhui Hu Wenhui Hu Guochun Jiang Guochun Jiang Microglia-Specific Promoter Activities of HEXB Gene Frontiers in Cellular Neuroscience HexB CD68 microglia astrocytes gene therapy gene editing |
| title | Microglia-Specific Promoter Activities of HEXB Gene |
| title_full | Microglia-Specific Promoter Activities of HEXB Gene |
| title_fullStr | Microglia-Specific Promoter Activities of HEXB Gene |
| title_full_unstemmed | Microglia-Specific Promoter Activities of HEXB Gene |
| title_short | Microglia-Specific Promoter Activities of HEXB Gene |
| title_sort | microglia specific promoter activities of hexb gene |
| topic | HexB CD68 microglia astrocytes gene therapy gene editing |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.808598/full |
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