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Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
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Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
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Journal Article
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
2016
Overview
AAV vectors that efficiently transduce the mouse brain after intravenous injection are generated with a CRE-dependent selection system.
Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for
in vivo
gene transfer
1
,
2
,
3
,
4
,
5
,
6
. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics
7
,
8
,
9
,
10
,
11
,
12
,
13
. Here we describe a capsid selection method, called Cre recombination–based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations
in vivo
. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs.
14
,
15
,
16
,
17
), and transduces the majority of astrocytes and neurons across multiple CNS regions.
In vitro
, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications.
