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
This study developed a nonviral gene delivery system using RGDyC-modified PEGylated PAMAM dendrimers to condense plasmid DNA encoding recombinant hirudin (rHV) for thrombus-targeted gene therapy. In vitro, the RGDyC-modified dendrimer achieved approximately 7.56-fold higher transfection efficiency than lipofectamine 2000 in HUVEC cells, with peak hirudin fusion protein expression at an N/P ratio of 0.5. In a Wistar rat venous thrombosis model, the RGDyC-modified group showed reduced thrombus weight, with no significant difference compared to the heparin group (P > 0.05). For ASH's domain, this explores a gene therapy approach to deliver recombinant hirudin to thrombus sites. The abstract does not attribute hirudin to leech origin or describe it as a thrombin inhibitor. The caveat is that this is a preclinical proof-of-concept study in cells and rats with no human data, safety profiling, or comparison with clinically used hirudin formulations.
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
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026