Anti-angiogenic treatment of endometriosis via anti-VEGFA siRNA delivery by means of peptide-based carrier in a rat subcutaneous model

Development of gene therapy for endometriosis requires inhibition of vascularization in endometrial lesions. We have previously developed CXCR4 receptor-targeted siRNA carrier L1 and observed efficient RNAi-mediated down-regulation of VEGFA gene expression in endothelial cells followed by decrease in VEGFA protein production and inhibition of cell migration. In this study we evaluated L1 carrier as non-viral vector for anti-VEGFA siRNA delivery into endometrial implants in rat subcutaneous endometriosis model created by subcutaneous auto-transplantation of uterus horn’s fragments. Therapeutic anti-angiogenic efficiency of anti-VEGFA siRNA/L1 polyplexes was evaluated by lesion size measurement, histopathologic examination, immunohistochemical staining and real-time reverse transcriptase-PCR analysis. After in vivo administration of anti-VEGFA siRNA we observed a 55–60% inhibition of endometriotic lesions growth and approximately two-fold decrease in VEGFA gene expression in comparison with untreated implants. Results of immunohistochemical examination of endometriotic lesions confirmed anti-angiogenic effects of anti-VEGFA siRNA/L1 polyplexes. Ultimately, our results demonstrate the efficiency of anti-angiogenic treatment of EM by means of anti-VEGFA siRNA delivery with L1 peptide-based carrier. This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 6 print issues and online access 251,40 € per year only 41,90 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Similar content being viewed by others

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We are thankful to Tatyana Kleimenova for technical assistance and Sara Gjurgji for English correction of the article. This work was supported by Russian Science Foundation grant 14-15-00737. Also we acknowledge partial financial support of peptide synthesis and antibody expenses by Russian Foundation for Basic Research grants 15-04-00591 and 18-015-00357. Marianna Maretina is supported by President of Russian Federation scholarship (SP-822.2018.4). Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Rights and permissions About this article Cite this article Egorova, A., Petrosyan, M., Maretina, M. et al. Anti-angiogenic treatment of endometriosis via anti-VEGFA siRNA delivery by means of peptide-based carrier in a rat subcutaneous model. Gene Ther 25, 548–555 (2018). https://doi.org/10.1038/s41434-018-0042-7 Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1038/s41434-018-0042-7 This article is cited by - Endometriosis MDC: role of the radiologist Abdominal Radiology (2025) - Delivery technologies for women’s health applications Nature Reviews Bioengineering (2023)