Blood: The activity of the VIII factor produced by genetically modified in human plasma after AAV5 gene therapy.

Gene therapy based on adeno-related viruses (AAVs) can restore the expression of hemophilia A (HA) endogenetic factor VIII (FVIII).
AAV vectors typically utilize FVIII genetically modified organisms missing from the B domain, such as the human FVIII-SQ in the valoccogene roxparvovec (AAV5-FVIII-SQ).
FVIII activity in two independent trials was surprisingly high, the activity of FVIII-SQ produced by GM in stage I blood clots (OS) was 1.3-2.0 times higher than that of the hair color substrate (CS), while the OS activity of recombinant FVIII-SQ was lower than CS.
in CS experiments, GM FVIII-SQ had similar specific activities (IU/mg) with recombinant FVIII-SQ, indicating that different activities appeared in OS experiments.
of FVIII-SQ produced by GM has been observed in different test kits and clinical laboratories with different activity of healthy ligenes FVIII, indicating that the underlying molecular characteristics are the underlying cause.
further experiments in two subjects showed that FVIII-SQ produced by GM accelerated the formation of early factors Xa and clotting enzymes, which may explain the higher OS activity based on the dynamic deviation between OS and CS detection read time.
although clotting began faster, the overall level of clotting enzymes was not affected.
correlation between blood and joint bleeding shows that OS and CS testing are still clinically significant in distinguishing between haemophilia and non-haemophilia FVIII activity levels.
during clinical development, CS activity was selected as an alternative endpoint to conservatively evaluate hemostase and to be able to compare with recombinant FVIII-SQ products.
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