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Technical requirements for effective regional hydrodynamic gene delivery to the left lateral lobe of the rat liver

Abstract

Hydrodynamic gene delivery to the liver is an attractive approach for clinical liver gene therapy, but critical aspects of technique remain uncertain. There has not been to date any report of high levels of hydrodynamic gene delivery to the liver, except in rodents. Regional hydrodynamic delivery to individual lobes/segments of the liver is being pursued in preclinical pig models, where reporter gene expression has been <1% of rodent levels, and in one clinical study, where there was no substantive evidence of gene expression. In none of these studies did surgical technique include outflow obstruction of the DNA solution. Here we report a novel technique for regional hydrodynamic gene delivery to the left lateral lobe of the rat liver. The technique gives high levels of gene delivery specific to the left lateral lobe with low volumes (1.5 ml) of DNA solution, and permits an evaluation of hydrodynamic delivery in the presence and in the absence of outflow obstruction. We report that outflow obstruction is an absolute requirement for effective hydrodynamic gene delivery to individual lobes/segments of the liver, and therefore that minimally invasive techniques will not be possible in the clinic.

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Acknowledgements

We acknowledge the support from the Rosetrees Trust.

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Correspondence to J W Fabre.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on Gene Therapy website

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Supplementary Information 1

Technique for hydrodynamic gene delivery to the left lateral lobe of the liver in the rat. (MPG 264663 kb)

Supplementary Information 2

Hydrodynamic gene delivery WITHOUT outflow obstruction. (MPG 10646 kb)

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Sawyer, G., Zhang, X. & Fabre, J. Technical requirements for effective regional hydrodynamic gene delivery to the left lateral lobe of the rat liver. Gene Ther 17, 560–564 (2010). https://doi.org/10.1038/gt.2009.167

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