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Gene Ther. 2018 Dec;25(8):548-555. doi: 10.1038/s41434-018-0042-7. Epub 2018 Sep 25.

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

Author information

1
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line, 3, Saint-Petersburg, 199034, Russia.
2
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line, 3, Saint-Petersburg, 199034, Russia. ankiselev@yahoo.co.uk.

Abstract

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.

PMID:
30254304
DOI:
10.1038/s41434-018-0042-7
[Indexed for MEDLINE]

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