Titer determination of Ad5 in blood: a cautionary note

Gene Therapy
G CichonP Pring-Akerblom

Abstract

Recombinant adenoviruses are presently the most efficient in vivo gene transfer system available. Targeting single organs or large tumors by adenoviral vectors requires an intravascular route of application. During the first pass of viral particles through the vascular bed of the target tissue, virus uptake is not quantitative and indefinite amounts of particles leak into circulation. To determine the amount of leaking particles and to calculate organ-specific uptake (in-/outflow ratio), it is necessary to titrate virus particles directly in blood. In preclinical and clinical trials titration is currently mostly done with blood plasma instead of full blood. However, this technique provides valid results only as long as there is no affinity between adenovirus particles and erythrocytes. In this study we demonstrate that Ad5 particles, as mostly employed for gene therapy, have a strong affinity to human erythrocytes. At 60 min after coincubation of human erythrocytes and Ad5 particles, more than 98% of the particles are attached to the surface of erythrocytes. Therefore, ignoring the amount of red cell bound particles by performing titration in plasma leads to severe miscalculation of organ-specific transfer rates or virus circul...Continue Reading

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Citations

Sep 9, 2010·Molecular Pharmaceutics·Piyanuch WongananMaria A Croyle
May 17, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andrew H BakerDmitry M Shayakhmetov
Nov 21, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andrew H Baker
Mar 30, 2005·Journal of Virology·Daniel StoneAndré Lieber
Jun 16, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·L KrutzkeF Kreppel
Aug 6, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Campbell G NicolAndrew H Baker
Apr 4, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mark LyonsKerry D Fisher
Jan 11, 2008·Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz·C Spitzer, H J Freyberger
Jun 20, 2020·Human Gene Therapy·Lea KrutzkeStefan Kochanek
Jan 17, 2020·FEBS Letters·Michael A BarryShao-Chia Lu
Sep 14, 2020·Cancer Gene Therapy·Sadia ZafarAkseli Hemminki
Mar 7, 2021·International Journal of Molecular Sciences·Florian Kreppel, Claudia Hagedorn

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