Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy
Basic science / gene therapy published in Mol Pharm (2019)
Abstract
This study proposed a new nonviral gene delivery system for thrombus targeting therapy based on PEGlyation polyamides dendrimer (PAMAM) modified with RGDyC to condense the pDNA with recombinant hirudine (rHV) gene (RGDyC-rHV-EGFP). The RGDyC-mPEG-PAMAM was synthesized and characterized by 1H NMR, PAMAM/pDNA was characterized by particle size, zeta potential, cellular uptake, and gel retraction assay. The transfection was carried out between lipofectamine 2000 and PAMAM/pDNA on HUVEC cells at various N/P ratios. The antithrombotic effect in vivo was evaluated by venous thrombosis model on Wistar rats. It showed that the drug delivery system of RGDyC modified PAMMA, which entrapped pDNA could significantly improve the transfection efficiency. It was about 7.56-times higher than that of lipofectamine 2000. In addition, the expression level of hirudine fusion protein was the highest at N/P ratio of 0.5. The results of antithrombotic effect showed that the weight of thrombus was reduced in RGDyC modified group; compared with heparin group, there was no significant difference ( P > 0.05). Overall, we take the advantage of the unique advantages of hirudine, combining the genetic engineering, nanocarriers, and targeting technology, to achieve the targeted enrichment and activation the hirudine fusion protein in the thrombus site, to improve the concentration of drugs in the thrombus site, finally increasing the curative effect and reduce the risk of bleeding. The strategy of gene delivery system holds unique properties as a gene delivery system and has great promises in thrombus targeting therapy.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
RGDyC-modified PEGylated PAMAM dendrimer condensing a recombinant hirudine pDNA-EGFP plasmid for thrombus-targeted gene delivery. Achieves 7.56-fold higher transfection efficiency than lipofectamine 2000 in HUVEC cells with effective antithrombotic activity in rats.
Por qué esto importa para la hirudoterapia
Este estudio desarrolló un sistema de administración génica no viral utilizando dendrímeros PAMAM pegilados modificados con RGDyC para condensar ADN plasmídico que codifica hirudina recombinante (rHV) para terapia génica dirigida a trombos. In vitro, el dendrímero modificado con RGDyC alcanzó una eficiencia de transfección aproximadamente 7,56 veces mayor que la de lipofectamina 2000 en células HUVEC, con una expresión pico de la proteína de fusión de hirudina a una relación N/P de 0,5. En un modelo de trombosis venosa en ratas Wistar, el grupo modificado con RGDyC mostró una reducción del peso del trombo, sin diferencia significativa en comparación con el grupo de heparina (P > 0,05). Para el dominio de la ASH, esto explora un enfoque de terapia génica para administrar hirudina recombinante a los sitios de trombosis. El resumen no atribuye la hirudina a origen de sanguijuela ni la describe como inhibidor de la trombina. La limitación es que se trata de un estudio preclínico de prueba de concepto en células y ratas, sin datos en humanos, sin perfil de seguridad ni comparación con formulaciones de hirudina de uso clínico.
Citación
Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy.
Chen J et al. · Molecular pharmaceutics, 2019
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026