Anti-angiogenic treatment of endometriosis via anti-VEGFA siRNA delivery by means of peptide-based carrier in a rat subcutaneous model.
Gene Ther
; 25(8): 548-555, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30254304
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Técnicas de Transferencia de Gen
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Factor A de Crecimiento Endotelial Vascular
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Endometriosis
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Tratamiento con ARN de Interferencia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article