Is it possible that rAAV vectors (while carrying some fluorescent tags) still cross synapses and pass from one neuron to the other? Any evidence, publication on this issue?
Adeno-associated viruses are replication-incompetent and therefore should not jump; is the tag found very far away from the injection site? Sometimes during injection there is a spill-over of the virus in the csf (you do not see it when injecting intracranially) and aavs can spread via the csf.
There are a couple of reports describing retrograde transport in the brain, e.g. in following recent paper showing specific transport of AAV5. "Analysis of Transduction Efficiency, Tropism and Axonal Transport of AAV Serotypes 1, 2, 5, 6, 8 and 9 in the Mouse Brain" Aschauer DF et al.
Although AAVs mainly infect neurons via cell bodies, there are few reports that some AAV serotypes could infect neurons via synapse and thus retrogradely label neuronal cell bodies that are far away from the injection site. However, no reports showing that AAVs "jump" through the synapse. But recombinant rabies do, check papers from Ed Callaway lab.
Theorically, as Francesco Roselli and Konstantin Khodosevich mentioned, AAVs shouldn't jump, although I have some observationswhich are difficult to explain on this basis. I inject AAV5 in vivo - in CA1 hippocampal area and 15 days after I have fluorescent cells only in this region. I questioned myself what happens if I wait longer, so I waited 2-4 months after injection and I've checked the infection - all hippocampus was fluorescent - not only CA1 but also CA3 and DG.
Usually, a helper dependent mobilization or translocation is required.
I would like to refer you to the authors of this paper
Giovanni Di Pasquale: [email protected]
and Jay Chiorini: [email protected]
I am sure you will get a satisfying answer.
Molecular Therapy (2006) 13, 506–516; doi: 10.1016/j.ymthe.2005.11.007
AAV Transcytosis through Barrier Epithelia and Endothelium
Giovanni Di Pasquale1 and John A. Chiorini1
1Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
Correspondence: John A. Chiorini, NIH 10/1N113, 10 Center Drive, MSC1190, Bethesda, MD 20892, USA. Fax: +1 301 402 1228. E-mail: [email protected]
Received 18 July 2005; Revised 8 November 2005; Accepted 8 November 2005.
Thanks for all the answers. They were very valuable.
I know that we should not see transsynaptic AAV movement. However, we occasionally experience anomalies similar to those Paula mentioned. I just wanted to know if I'm alone with this? And what is the commonly accepted view on these?
Benjamin and Ingo, thanks for the references!
check this paper and several of its references-
PLoS One. 2013 Sep 27;8(9):e76310. doi: 10.1371/journal.pone.0076310. eCollection 2013.
Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain.
Aschauer DF1, Kreuz S, Rumpel S.
Check this update (Brian Zingg et al., 2017).
"Here, we report that adeno-associated virus (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties."
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538794/
Title: AAV-mediated Anterograde Transsynaptic Tagging: Mapping Input-Defined Functional Neural Pathways for Defense Behavior.
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