Hepatic control elements promote long‐term expression of human coagulation factor IX gene in hydrodynamically transfected mice

Kim, Hong Sung; Kim, Jong Chul; Lee, Yeon Kyung; Kim, Jung Seok; Park, Yong Serk

doi:10.1002/jgm.1583

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…They reported therapeutic plasma levels of protein over six months and functional activity in the correction of bleeding after tail clipping. Likewise, in 2011, Kim et al [ 34 ] reported long-term expression of hFIX (above 500 ng/mL) and clotting activity for seven months in FIX knockout mice after hydrodynamic injection without genome integration. Given the positive outcomes obtained, researchers evaluated gene constructions with greater potential to be employed in humans.…”

Section: Gene Transfer Applicationsmentioning

confidence: 99%

Translational Advances of Hydrofection by Hydrodynamic Injection

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2018

Genes

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Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.

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Section: Gene Transfer Applicationsmentioning

confidence: 99%

Translational Advances of Hydrofection by Hydrodynamic Injection

Sendra

Herrero

Aliño

2018

Genes

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“…transfer of the FIX gene in vivo is possible even by the naked plasmid DnA, as has been shown in animal models. Hydrodynamic injection of expression plasmid containing human FIX cDnA and the hepatic control region was sufficient to achieve therapeutic levels of FIX in deficient mice for 210 days [75]. the delivery technique employed -injection of 50 µg of the plasmid in 2 ml of solution in 5-8 sec into the tail vein -is definitely unsuitable for human therapy, and a significant modification of hydrodynamic injection should be invented before clinical studies can take place.…”

Section: Gene Therapy Of Hemophilia Bmentioning

confidence: 99%

Coagulation Factor IX for Hemophilia B Therapy

et al. 2012

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Factor IX is a zymogen enzyme of the blood coagulation cascade. Inherited absence or deficit of the IX functional factor causes bleeding disorder hemophilia B, which requires constant protein replacement therapy. Reviewed herein are the current state in the manufacturing of FIX, improved variants of the recombinant protein for therapy, transgenic organisms for obtaining FIX, and the advances in the gene therapy of hemophilia B.

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“…Hydrodynamic injection of expression plasmid containing human FIX cDNA and the hepatic control region was sufficient to achieve therapeutic levels of FIX in deficient mice for 210 days [75]. The delivery technique employed – injection of 50 µg of the plasmid in 2 ml of solution in 5-8 sec into the tail vein – is definitely unsuitable for human therapy, and a significant modification of hydrodynamic injection should be invented before clinical studies can take place.…”

Section: Gene Therapy Of Hemophilia Bmentioning

confidence: 99%