The ubiquitous chromatin opening element from the human HNRPA2B1-CBX3 housekeeping
gene locus (A2UCOE) is able to provide stable and cell-to-cell reproducible levels of transgene expression
regardless of target cell genome integration site with efficacy demonstrated in adult, embryonic and
induced pluripotent stem cells and their differentiated progeny in vitro and in vivo. Here we evaluate the
ability of A2UCOE-based lentiviral vectors to confer stable expression following pre-natal delivery in
mice. Our results show stable post-natal A2UCOE-eGFP and A2UCOE-luciferase lentiviral vector
presence in both the liver and haematopoietic system with concomitant persistence of expression demonstrating
efficient transduction of both fetal liver and haematopoietic stem cells. In addition, we find
that an A2UCOE-FIX lentiviral vector produces comparable amounts of plasma FIX protein to that obtained
from a SFFV-FIX construct. Furthermore, the A2UCOE-FIX vector shows that at a low (0.19)
average vector copy number per liver cell, it can provide stable levels of plasma FIX production, which
would convert severe haemophilia B (<1%) to a mild phenotype (≈20%). Our results provide proof-ofprinciple
for low dose pre-natal A2UCOE-based LV delivery to the liver as a therapeutic option for
haemophilia B and potentially other metabolic conditions.
Keywords: UCOE, Haemophilia B, Lentiviral vectors, Pre-natal, Gene therapy.
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