Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous…

By Corinna Burger, O. Gorbatyuk, M. J. Velardo, Carmen S. Peden, P. Williams, S. Zolotukhin, P. Reier, R. Mandel, N. Muzyczka. Molecular Therapy, 2004

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Recombinant adeno-associated virus 2 (rAAV2) has been shown to deliver genes to neurons effectively in the brain, retina, and spinal cord. The characterization of new AAV serotypes has revealed that they have different patterns of transduction in diverse tissues. We have investigated the tropism and transduction frequency in the central nervous system (CNS) of three different rAAV vector serotypes. The vectors contained AAV2 terminal repeats flanking a green fluorescent protein expression cassette under the control of the synthetic CBA promoter, in AAV1, AAV2, or AAV5 capsids, producing the pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5. Rats were injected with rAAV2/1, rAAV2/2, or rAAV2/5 into selected regions of the CNS, including the hippocampus (HPC), substantia nigra (SN), striatum, globus pallidus, and spinal cord. In all regions injected, the three vectors transduced neurons almost exclusively. All three vectors transduced the SN pars compacta with high efficiency, but rAAV2/1 and rAAV2/5 also transduced the pars reticulata. Moreover, rAAV2/1 showed widespread distribution throughout the entire midbrain. In the HPC, rAAV2/1 and rAAV2/5 targeted the pyramidal cell layers in the CA1-CA3 regions, whereas AAV2/2 primarily transduced the hilar region of the dentate gyrus. In general, rAAV2/1 and rAAV2/5 exhibited higher transduction frequencies than rAAV2/2 in all regions injected, although the differences were marginal in some regions. Retrograde transport of rAAV1 and rAAV5 was also observed in particular CNS areas. These results suggest that vectors based on distinct AAV serotypes can be chosen for specific applications in the nervous system.

Subfields: Cardiology and Cardiovascular Medicine, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bac4c41d5cfea96e922f91784d1746458ec2d4da

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Citations in the corpus

Adeno-associated virus serotypes: vector toolkit for human gene therapy. (2006, background): “In general, AAV1 and 5 exhibit higher transduction frequencies than AAV2 in all regions injected within the CNS [64,65].”
Functional imaging of hippocampal place cells at cellular resolution during virtual navigation (2010, positive): “Hippocampal injections of adeno-associated virus AAV2/1-synapsin-1 -GCaMP3 (a moderate, neuron-specific promoter 18 in a serotype with efficient gene delivery to neurons 19 ) resulted in expression of GCaMP3 in a large population of CA1 neurons.”
Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors (2010, positive): “AAV5 has revealed higher transduction frequencies than AAV2 within the central nervous system (Burger et al. , 2004) and arthritic joints (Khoury et al. , 2007).”
Molecular and cellular approaches for diversifying and extending optogenetics. (2010, result): “…2008), and indeed virtually all viruses (including AAVs) carry some degree of this capability in a serotype- and circuit-dependent manner, as we and others have observed (Burger et al., 2004; Paterna et al., 2004; Callaway, 2008; Lima et al., 2009; Passini et al., 2005; Nathanson et al., 2009).”