Systemic Gene Delivery by Single-Dose Intracardiac Administration of scAAV2/9 and scAAV2/rh10 Variants in Newborn Rats

Abstract

Recombinant adeno-associated virus serotype 9 (rAAV2/9) and pseudotype rhesus-10 (rAAV2/rh10) are used for gene delivery, especially into the central nervous system. Both serotypes cross the blood-brain barrier and mediate stable long-term transduction in dividing and nondividing cells. Among possible routes of administration, intracardiac injection holds the potential for widespread vector diffusion associated with a relatively simple approach. In this study adopting the intracardiac route, we compare the cell-specific tropism and transfection efficacy of a panel of engineered rAAV2/9 and rAAV2/rh10 vectors encoding the enhanced green fluorescent protein. We observed transduction in the brain and peripherally, with a predominant neuronal tropism while the various serotypes achieved different expression patterns.

Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques

“…Since both serotypes share the ability to cross the blood-brain barrier (BBB) in newborns, they may be delivered through various administration routes ( Bourdenx et al, 2014 ; Bedbrook et al, 2018 ). They are associated with widespread, long-term transduction in nondividing cells in rodents ( Cearley and Wolfe, 2006 ; Duque et al, 2009 ; Foust et al, 2009 ; Zhang et al, 2011 ; Chansel-Debordeaux et al, 2017 ; Chansel-Debordeaux et al, 2018 ) and non-human primates (NHPs) ( Dehay et al, 2012 ; Gray et al, 2013 ; Samaranch et al, 2013 ; Hinderer et al, 2014 ; Yang et al, 2014 ; Bey et al, 2020 ), making them a powerful tool for delivering genetic material to the CNS. Recently, a novel AAV9-derived variant that far more efficiently crosses the mouse BBB (named AAV-PHP.…”