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).
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
|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|
|20298||pAAV-EF1a-double floxed-hChR2(H134R)-EYFP-WPRE-HGHpA||EF1a||Activator, Cre-dependent||ChR2||Deisseroth|
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
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
When using the PHP serotypes in future publications, please acknowledge Viviana Gradinaru and cite Chan et al., Nat Neurosci, 20(8):1172-1179. Pubmed.
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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.