AAV-PHP.eB Peripheral Delivery and Central Expression in Cre Mice.
Haidong Zhu1, Joel C Geerling1,2
1Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
The Journal of Comparative Neurology
|December 31, 2025
Summary
Peripheral delivery of PHP.eB virus can target widespread neurons, but efficiency varies by brain region and cell type. Careful consideration is needed for specific neuronal population research.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Investigating neuronal populations is crucial for neuroscience.
- Stereotaxic injections target specific brain regions but not widespread populations.
- PHP.eB virus can cross the blood-brain barrier via peripheral injection.
Purpose of the Study:
- To evaluate the tropism and transduction efficiency of PHP.eB virus for different neuronal populations.
- To determine if PHP.eB transduces neurons equally across various brain regions.
Main Methods:
- Retro-orbital injections of a PHP.eB vector encoding a Cre-dependent reporter.
- Utilized various Cre-driver mouse lines.
- Examined brains for reporter gene expression to assess transduction.
Main Results:
- Observed significant variability in transduction efficiency across different brain regions and neuronal cell types.
- Detected scattered neuron and astrocyte transduction in all Cre-driver strains.
- Found low-level spontaneous recombination in Cre-negative controls.
Conclusions:
- Peripheral PHP.eB delivery successfully targets widely distributed neuronal populations.
- Variations in tropism, sensitivity, and specificity necessitate careful planning for specific neuronal targeting.
- PHP.eB shows promise for broad neuronal access but requires population-specific validation.
Keywords:
11‐beta‐hydroxysteroid dehydrogenase type 2 (HSD2)Foxp2Hsd11b2Lmx1bPHP.eBgene therapyneuropeptide SMore Related Videos
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