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The neonatal blood-brain barrier is functionally effective, and immaturity does not explain differential targeting of AAV9

Nature Biotechnology volume 27, pages 804–805 (2009)Cite this article

To the Editor:

In the January issue, Foust et al.1 reported the interesting finding that adeno-associated virus (AAV) 9, when injected intravenously, targets different cell types in the brain in an age-dependent manner. When injected into neonatal mice (1 day old, P1), AAV9 was predominantly distributed in neurons, whereas in adult mice, it was mainly found in astrocytes. The authors make several unreferenced statements about the blood-brain barrier (BBB) in neonates—“not fully developed,” “before the closure of the BBB”—and suggest that immaturity of the BBB accounts, at least in part, for the age-related difference in cellular uptake. The authors do not state what aspect of BBB mechanisms they consider not fully developed, although they mention in their Discussion that “Normally, tight junctions severely restrict penetration of the BBB by molecules and viruses.” If this is the barrier mechanism that they have in mind, they are incorrect. Although it is widely stated that the BBB is immature or incompletely formed in neonates, the tight junctions between cerebral endothelial cells (the morphological basis for BBB impermeability) are functionally effective as soon as the first blood vessels penetrate the parenchyma of the developing brain2,3.

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  1. Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia

    Norman R Saunders, C Joakim Ek & Katarzyna M Dziegielewska

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  1. Norman R Saunders
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  2. C Joakim Ek
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  3. Katarzyna M Dziegielewska
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Correspondence to Norman R Saunders.

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Saunders, N., Joakim Ek, C. & Dziegielewska, K. The neonatal blood-brain barrier is functionally effective, and immaturity does not explain differential targeting of AAV9. Nat Biotechnol 27, 804–805 (2009). https://doi.org/10.1038/nbt0909-804

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