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viral-icon-01.png Viral Service: Viviana Gradinaru PHP AAV Serotypes


As part of our Viral Service, Addgene is distributing ready-to-use viral preparations in the PHP.eB, PHP.S, and PHP.V1 serotypes from the Viviana Gradinaru laboratory and the Caltech CLOVER Center. As part of our standard viral production, these viral vectors undergo quality control, including AAV titering by probe-based droplet digital PCR, in vitro and (when possible) in vivo testing, and full sequencing of the final viral vector preparation.

Systemic Delivery AAV Capsid Choice

Need help deciding which capsid to choose? The following decision tree was developed with help from Tim Miles of the Clover Center and can help guide your decision. Note that you should use the CAG ubiquitous promoter for strongest expression unless specified for cell type selectivity. All capsids also show some off-target tissue or organ transduction, however, PHP.N and CAP-B10 are markedly de-targeted from the periphery. See capsid publications for more details (Chan et al. Nat Neurosci. 2017, Kumar et al. Nat Methods. 2020).

AAV decision tree. Described under the heading Text Description for the AAV Decision Tree
Decision Tree for choosing your AAV capsid.

Follow the tree to find your cell type. The recommended capsid is listed first in bold red, with an alternative listed second in grey. *PHP.B, eB, V1, and N capsids all operate via the protein Ly-6a. Please confirm that it is present in your murine strain. PHP.B and eB have been validated in Sprague Dawley, Long-Evans, and Fischer rats. B10 and B22 Capsids are currently not available at Addgene. Text version of the AAV decision tree can be found at the bottom of this page.

PHP.eB

These viral vector preparations were produced with the pUCmini-iCAP-PHP.eB plasmid (Addgene #103005).

The PHP.eB serotype exhibits efficient transduction of the central nervous system via systemic delivery in adult animals. In vivo studies showed that, compared to PHP.B and AAV9, intravenous injection of PHP.eB AAV led to an increase in both the number of transduced cells and the expression level per cell. In vivo, PHP.eB transduced the majority of neurons in the cortex and striatum, and over 75% of cerebellar Purkinje cells.

Note on PHP.eB tropism and specific mouse lines: Enhanced CNS tropism exhibited by the PHP.eB serotype has been reported to occur through the cellular receptor LY6A (DOI 538421). For information on whether the PHP.eB serotype will work in your mouse line, see Supplementary Table 3.

Browse Available PHP.eB AAV

ID Name Promoter Description Category PI
Controls
28306 pAAV-FLEX-tdTomato CAG tdTomato, Cre-dependent Control Boyden
37825 pAAV-CAG-GFP CAG GFP Control Boyden
59462 pAAV-CAG-tdTomato CAG tdTomato Control Boyden
104061 CAG-NLS-GFP CAG NLS-GFP Control Gradinaru
Chemogenetics
44361 pAAV-hSyn-DIO-hM3D(Gq)-mCherry Syn1 Activator, Cre-dependent DREADD Roth
44362 pAAV-hSyn-DIO-hM4D(Gi)-mCherry Syn1 Inhibitor, Cre-dependent DREADD Roth
Biosensors
104491 pGP-AAV-syn-FLEX-jGCaMP7s-WPRE Syn Calcium sensor, Cre-dependent GCaMP Kim, GENIE
104492 pGP-AAV-syn-FLEX-jGCaMP7f-WPRE Syn Calcium sensor, Cre-dependent GCaMP Kim, GENIE
104487 pGP-AAV-syn-jGCaMP7s-WPRE Syn Calcium sensor GCaMP Kim, GENIE
104488 pGP-AAV-syn-jGCaMP7f-WPRE Syn Calcium sensor GCaMP Kim, GENIE
100854 pAAV.Syn.NES-jRGECO1a.WPRE.SV40 Syn Calcium sensor RGECO Kim, GENIE
Optogenetics
26973 pAAV-hSyn-hChR2(H134R)-EYFP Syn Activator ChR2 Deisseroth
20298 pAAV-EF1a-double floxed-hChR2(H134R)-EYFP-WPRE-HGHpA EF1a Activator, Cre-dependent ChR2 Deisseroth
127090 pAAV-CAG-DIO-ChR2(H134R)-eYFP CAG Activator, Cre-dependent ChR2 Gradinaru
Recombinases
105540 pENN.AAV.hSyn.HI.eGFP-Cre.WPRE.SV40 Syn Cre-EGFP expression Cre Wilson
105550 pAAV.GFAP.Cre.WPRE.hGH GFAP Cre-expression Cre Wilson

PHP.S

These viral vector preparations were produced with the pUCmini-iCAP-PHP.S plasmid (Addgene #103006).

The PHP.S serotype exhibits efficient transduction of the peripheral nervous system via systemic delivery in adult animals. In vivo studies showed that, relative to parent capsid AAV9, intravenous injection of PHP.S AAV led to an increase in both the number of transduced cells and the expression level per cell. PHP.S AAV was also shown to transduce neurons in the enteric nervous system and in other peripheral ganglia, such as the cardiac ganglia. When used with Cre transgenic lines or cell-type-specific promoters, this serotype could enable targeted transduction of subsets of cells within these regions.

Browse Available PHP.S AAV

ID Name Promoter Description Category PI
28306 pAAV-FLEX-tdTomato CAG tdTomato, Cre-dependent Control Boyden
59462 pAAV-CAG-tdTomato CAG tdTomato Control Boyden

PHP.V1

These viral vector preparations were produced with the pUCmini-iCAP-PHP.V1 plasmid (Addgene #127847).

The PHP.V1 serotype exhibits efficient transduction of vesicular brain cells via systemic delivery in adult animals. In vivo studies showed that, compared to PHP.eB and AAV9, intravenous injection of PHP.V1 AAV led to a >40% increase in transduction of cortical brain vasculature. PHP.V1 AAV was also shown to transduce S100+ astrocytes, but is less efficient in astrocyte transduction than PHP.eB when used with an astrocyte specific promoter.

Browse Available PHP.V1 AAV

ID Name Promoter Description Category PI
104052 pAAV-CAG-DIO-EYFP CAG EYFP, Cre-dependent Control Gradinaru

Citation Information

When using the PHP serotypes in future publications, please acknowledge Viviana Gradinaru and cite Chan et al., Nat Neurosci, 20(8):1172-1179. Pubmed.

Don’t See What You’re Looking For?

Please let us know what you would like to see available in viral format. Please note this does not guarantee viral service, but lets us know what viruses would be helpful to the scientific community.

Text Description for the AAV Decision Tree

The AAV decision tree graphic above helps you choose the best capsid for your cell type. First, what organism are you using? For marmoset, if you want to target the CNS with a neuron bias, CAP-B10 is recommended. For marmoset CNS broad tropism, CAP-B22 is recommended. For marmoset PNS there are no AAV capsids recommended at this time. If you are working in a mouse, and are targeting the CNS with broad expression, PHP.eB is recommended, with PHP.B as an alternative choice. For targeting mouse CNS, the following capsids are recommended for cell-type specific targeting: Astrocytes--PHP.eB with promoter or CRE animal recommended, Neurons--CAP-B10 recommended, PHP.N as alternative, Vascular--PHP.V1 with promoter or CRE animal recommended, Microglia--None validated, and Oligodendrocytes--PHP.eB with promoter or CRE animal recommended.

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