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Fig. 4
ICV delivery of scAAV9-GFP at P2 results in the transduction of peripheral organs. Heterozygous SMN
7
mice were ICV injected with 1 × 10
11
genomic copies of scAAV9-GFP, and the peripheral organs were harvested
5 days postinjection. The organs of virus-injected and age-matched untreated control mice were placed side
by side, and the images were captured using a Leica M205 FA Stereomicroscope with the fi lter excitation of
450-490 nm and emission of 500-550 nm. GFP expression was detected in the liver (
a
), heart (
b
), lung (
c
),
muscle (
d
), and brain (
e
) of scAAV9-GFP-injected mice
ʔ
circulation system, IV injection was considered to be more sensible
and applicable. However, our results in which the rescue of SMA
phenotype by ICV injection was more effi cient than IV injection
[
24
] led us to assume that the leakiness of ICV injection at P2 (due
to immature state of the blood-brain barrier) results in the trans-
duction of the peripheral organs as well. To prove this hypothesis,
we ICV injected 1 × 10
11
genomic copies of scAAV9-GFP into the
heterozygous SMN
7 mice, harvested the brain and peripheral
organs 5 days postinjection, examined the expression of the GFP in
the whole organs, and compared to the organs of the age-matched
untreated control. Our results clearly demonstrate that through
ICV injection, scAAV9-GFP is capable of transducing the liver,
heart, lung, and muscle as well as brain (Fig.
4a-e
). The level of
GFP expression in the kidney was negligible (data not shown), and
a very insignifi cant level of autofl orescence was captured in all the
organs of untreated control mice except the liver (Fig.
4
). Based on
these results, the superiority of the ICV delivery to IV delivery can
be attributed to the fact that the virus reaches the spinal cord
directly leading to effi cient transduction (Fig.
3b
) and transduces
ʔ
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