Isolation of novel simian adenoviruses from macaques for development of a vector for human gene therapy and vaccines
IMPORTANCE: Adenoviruses are widely used in gene therapy and vaccine delivery. Due to the high prevalence of human adenoviruses (HAdVs), the pre-existing immunity against HAdVs in humans is common, which limits the wide and repetitive use of HAdV vectors. In contrast, the pre-existing immunity against simian adenoviruses (SAdVs) is low in humans. Therefore, we performed epidemiological investigations of SAdVs in simians and found that the SAdV prevalence was as high as 33.9%. The whole-genome sequencing and sequence analysis showed SAdV diversity and possible cross species transmission. One isolate with low level of pre-existing neutralizing antibodies in humans was used to construct replication-deficient SAdV vectors with E4orf6 substitution and E1/E3 deletion. Interestingly, we found that the E3 region plays a critical role in its replication in human cells, but the absence of this region could be compensated for by the E4orf6 from HAdV-5 and the E1 expression intrinsic to HEK293 cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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| Enthalten in: |
Journal of virology - 97(2023), 10 vom: 31. Okt., Seite e0101423 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lan, Wendong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 12.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1128/jvi.01014-23 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Isolation of novel simian adenoviruses from macaques for development of a vector for human gene therapy and vaccines |
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| 520 | |a IMPORTANCE: Adenoviruses are widely used in gene therapy and vaccine delivery. Due to the high prevalence of human adenoviruses (HAdVs), the pre-existing immunity against HAdVs in humans is common, which limits the wide and repetitive use of HAdV vectors. In contrast, the pre-existing immunity against simian adenoviruses (SAdVs) is low in humans. Therefore, we performed epidemiological investigations of SAdVs in simians and found that the SAdV prevalence was as high as 33.9%. The whole-genome sequencing and sequence analysis showed SAdV diversity and possible cross species transmission. One isolate with low level of pre-existing neutralizing antibodies in humans was used to construct replication-deficient SAdV vectors with E4orf6 substitution and E1/E3 deletion. Interestingly, we found that the E3 region plays a critical role in its replication in human cells, but the absence of this region could be compensated for by the E4orf6 from HAdV-5 and the E1 expression intrinsic to HEK293 cells | ||
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| 700 | 1 | |a Quan, Lulu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yiqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Ou, Junxian |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Biyan |e verfasserin |4 aut | |
| 700 | 1 | |a Mei, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Liqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Chengsong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chodosh, James |e verfasserin |4 aut | |
| 700 | 1 | |a Seto, Donald |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qiwei |e verfasserin |4 aut | |
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