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Updated: Jun 3, 2026
Convection Enhanced Delivery of Optogenetic Adeno-associated Viral Vector to the Cortex of Rhesus Macaque Under Guidance of Online MRI Images
Published on: May 23, 2019
Evaluation and optimization of the administration of a selectively replicating herpes simplex viral vector to the
E White1, A Bienemann, L Megraw
1Department of Neurosurgery, Frenchay Hospital, Bristol, UK.
Abstract:
The direct intraparenchymal administration of oncolytic viral vectors by convection-enhanced delivery (CED) represents a promising new treatment strategy for malignant gliomas. However, there is no evidence to suggest that oncolytic viruses as large as herpes simplex virus-1 (HSV-1) can be administered by CED, as this has not been systematically examined in an animal model. In this study, the administration of a herpes simplex viral vector, HSV1, has been evaluated in detail in the gray and white matter of both rat and pig models, using high flow-rate infusions, co-infusing heparin or preinfusing the tissue with an isotonic albumin solution. Rat HSV-1 infusions at both slow (0.5 μl min(-1)) and high infusion rates (2.5 μl min(-1)) led to extensive tissue damage and negligible cell transduction. Co-infusion with heparin led to extensive hemorrhage. Preinfusion of tissue with an isotonic albumin solution facilitated widespread vector distribution and cell transduction in white matter only. Using this approach in pig brain led to widespread vector distribution with extensive transduction of astrocytes and activated microglia. In rat brain, enhanced green fluorescent protein expression peaked 48 h after vector administration and was associated with a vigorous immune response. These findings indicate that direct infusions of HSV-1-based viral vectors into the brain lead to minimal vector distribution, negligible cell transduction and extensive damage. Tissue preinfusion with an isotonic solution prior to vector administration represents an effective technique for achieving widespread HSV-1 distribution.
Insights
Directly infusing herpes simplex virus-1 (HSV-1) vectors into the brain caused damage and poor cell transduction. Pre-treating brain tissue with an albumin solution improved HSV-1 distribution and transduction, especially in white matter.
Area of Science:
- Neuro-oncology
- Virology
- Biomedical Engineering
Background:
- Convection-enhanced delivery (CED) is a promising strategy for malignant glioma treatment using oncolytic viral vectors.
- The feasibility of administering large oncolytic viruses like herpes simplex virus-1 (HSV-1) via CED has not been systematically studied in animal models.
Purpose of the Study:
- To evaluate the safety and efficacy of direct intraparenchymal administration of HSV-1 viral vectors using CED in rat and pig models.
- To investigate methods for improving vector distribution and transduction in brain tissue.
Main Methods:
- HSV-1 viral vectors were administered via CED into rat and pig brains at varying infusion rates.
- Techniques explored included co-infusion with heparin and pre-infusion with an isotonic albumin solution.
- Tissue damage, vector distribution, and cell transduction (e.g., enhanced green fluorescent protein expression) were assessed.
Main Results:
- High-flow infusions of HSV-1 vectors in rats caused significant tissue damage and minimal cell transduction.
- Co-infusion with heparin resulted in extensive hemorrhage.
- Pre-infusion with an isotonic albumin solution enhanced vector distribution and transduction in white matter of rats and in astrocytes and microglia in pigs.
- Enhanced green fluorescent protein expression peaked at 48 hours post-administration in rats, accompanied by an immune response.
Conclusions:
- Direct CED infusion of HSV-1 vectors into the brain results in limited distribution, negligible transduction, and considerable tissue damage.
- Pre-infusion of brain tissue with an isotonic solution is an effective method to achieve widespread HSV-1 distribution and transduction, particularly in white matter.
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