Microvasculature-targeted therapeutic AAV vectors for selective brain delivery
This technology is an AAV-based gene delivery platform that selectively targets brain microvascular endothelial cells for the treatment of neurovascular and neurodegenerative diseases.
Unmet Need: Selective and efficient gene delivery to brain microvasculature
Current gene therapy approaches for central nervous system diseases largely rely on vectors that preferentially transduce neurons or exhibit broad, non-specific distribution following systemic delivery. Existing viral vectors targeting brain endothelial cells exhibit limited efficiency, poor selectivity, and inconsistent performance across animal strains and species, particularly in primates, thereby restricting their translational potential. As a result, therapeutic strategies aimed at correcting brain endothelial dysfunction or leveraging endothelial cells as therapeutic production sites remain largely impractical. Addressing these limitations is critical for enabling effective, safe, and translatable treatments for neurovascular and endothelial-driven neurological diseases.
The Technology: AAV-mediated microvascular targeting for neurovascular and neurodegenerative disease therapy
This technology enables specific and efficient targeting of the brain microvasculature by leveraging the natural tropism of select adeno-associated viral (AAV) serotypes for brain endothelial cells. Following systemic administration, these vectors preferentially transduce endothelial cells that form the blood–brain barrier while largely avoiding neurons and glial cells within the brain parenchyma. Thus, this system can be used to deliver therapeutic material for correcting genetic disorders. For example, delivery of the non-coding RNA SLC2A1-NAT or a functional version of the Glut1 gene can restore glucose transport activity across the blood-brain barrier. Therefore, this cell-type specific modality provides a non-invasive strategy for treating Glut1-related syndromes, as well as other neurovascular and neurodegenerative conditions.
This technology has been validated in multiple rodent and non-human primate models using systemic in vivo delivery.
Applications:
- Gene therapy for neurovascular and neurodegenerative diseases
- Treatment of Glucose Transporter-1 Deficiency Syndrome (Glut1DS)
- Therapeutic delivery for lysosomal storage disorders affecting the central nervous system (e.g. Gaucher’s, Hurler’s, Hunter’s, Fabry diseases)
- Systemic therapeutics delivery to the brain microvasculature with minimal off-target transduction
- Research tool for studying brain endothelial biology and neurovascular function in vivo
- Preclinical development platform for evaluating endothelial-focused CNS therapeutics
Advantages:
- Highly selective targeting of brain microvasculature
- Minimal off-target transduction of neurons and glia
- Systemic, non-invasive delivery
- Improved efficiency over existing AAV vectors
- Robust and consistent performance across multiple in vivo models
- Compatible with standard AAV manufacturing
Lead Inventor:
Patent Information:
Patent Pending (WO/2025/137149)
Related Publications:
Tech Ventures Reference:
IR CU24146
Licensing Contact: Kristin Neuman