Academic Journal
Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1
| العنوان: | Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1 |
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| المؤلفون: | Vermeulen, Christie, Brachtlova, Tereza, Tol, Nikki, van der Meulen-Muileman, Ida H., Hodzic, Jasmina, van de Vrugt, Henri J., van Beusechem, Victor W. |
| المصدر: | Vermeulen , C , Brachtlova , T , Tol , N , van der Meulen-Muileman , I H , Hodzic , J , van de Vrugt , H J & van Beusechem , V W 2022 , ' Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1 ' , International Journal of Molecular Sciences , vol. 23 , no. 23 , 15430 . https://doi.org/10.3390/ijms232315430 |
| سنة النشر: | 2022 |
| الوصف: | Oncolytic adenoviruses are promising new anticancer agents. To realize their full anticancer potential, they are being engineered to express therapeutic payloads. Tumor suppressor p53 function contributes to oncolytic adenovirus activity. Many cancer cells carry an intact TP53 gene but express p53 inhibitors that compromise p53 function. Therefore, we hypothesized that oncolytic adenoviruses could be made more effective by suppressing p53 inhibitors in selected cancer cells. To investigate this concept, we attenuated the expression of the established p53 inhibitor synoviolin (SYVN1) in A549 lung cancer cells by RNA interference. Silencing SYVN1 inhibited p53 degradation, thereby increasing p53 activity, and promoted adenovirus-induced A549 cell death. Based on these observations, we constructed a new oncolytic adenovirus that expresses a short hairpin RNA against SYVN1. This virus killed A549 cells more effectively in vitro and inhibited A549 xenograft tumor growth in vivo. Surprisingly, increased susceptibility to adenovirus-mediated cell killing by SYVN1 silencing was also observed in A549 TP53 knockout cells. Hence, while the mechanism of SYVN1-mediated inhibition of adenovirus replication is not fully understood, our results clearly show that RNA interference technology can be exploited to design more potent oncolytic adenoviruses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.3390/ijms232315430 |
| الاتاحة: | https://research.vumc.nl/en/publications/140e11da-7add-49b5-9aa5-cef11ebf7cbc https://doi.org/10.3390/ijms232315430 http://www.scopus.com/inward/record.url?scp=85143663612&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.EE1E861A |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/ijms232315430 |
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