In utero delivery of rAAV2/9 induces neuronal expression of the transgene in the brain: towards new models of Parkinson’s disease.
Gene Ther. 2017-11-16; 24(12): 801-809
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1. Gene Ther. 2017 Dec;24(12):801-809. doi: 10.1038/gt.2017.84. Epub 2017 Nov 16.
In utero delivery of rAAV2/9 induces neuronal expression of the transgene in the
brain: towards new models of Parkinson’s disease.
Chansel-Debordeaux L(1)(2)(3), Bourdenx M(1)(2), Dovero S(1)(2), Grouthier
V(1)(2), Dutheil N(1)(2), Espana A(4)(5), Groc L(4)(5), Jimenez C(1)(2)(3),
Bezard E(1)(2), Dehay B(1)(2).
(1)University de Bordeaux, Institut des Maladies Neurodégénératives Bordeaux,
(2)CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.
(3)CHU Bordeaux, Service de Biologie de la reproduction-CECOS, Centre Hospitalier
Universitaire de Bordeaux, Bordeaux, France.
(4)University de Bordeaux, Interdisciplinary Institute for Neuroscience,
(5)CNRS, Institut Interdisciplinaire de Neurosciences, Bordeaux, France.
Animal models are essential tools for basic pathophysiological research as well
as validation of therapeutic strategies for curing human diseases. However,
technical difficulties associated with classical transgenesis approaches in
rodent species higher than Mus musculus have prevented this long-awaited
development. The availability of viral-mediated gene delivery systems in the past
few years has stimulated the production of viruses with unique characteristics.
For example, the recombinant adeno-associated virus serotype 9 (rAAV2/9) crosses
the blood-brain barrier, is capable of transducing developing cells and neurons
after intravenous injection and mediates long-term transduction. Whilst
post-natal delivery is technically straightforward, in utero delivery bears the
potential of achieving gene transduction in neurons at embryonic stages during
which the target area is undergoing development. To test this possibility, we
injected rAAV2/9 carrying either A53T mutant human α-synuclein or green
fluorescent protein, intracerebroventricularly in rats at embryonic day 16.5. We
observed neuronal transgene expression in most regions of the brain at 1 and 3
months after birth. This proof-of-concept experiment introduces a new opportunity
to model brain diseases in rats.