AAV-ChP For Choroid Plexus Targeting

Choroid Plexus (ChP)

The choroid plexus (ChP) is a specialized vascular structure located within the brain’s ventricles. It plays a central role in producing cerebrospinal fluid (CSF) and maintaining the brain’s internal environment.

Key Features

  • Location: Found in the lateral, third, and fourth ventricles
  • Structure: Composed of a dense network of fenestrated capillaries surrounded by a layer of epithelial cells
  • Barrier function: Forms the blood–CSF barrier, which regulates the exchange of molecules between blood and CSF

Functions

  • CSF production: Responsible for ~70–80% of total CSF generation
  • Homeostasis: Maintains ionic balance and removes metabolic waste
  • Immune surveillance: Acts as an interface between the peripheral immune system and the central nervous system
  • Secretion: Produces growth factors, cytokines, and signaling molecules

Why It Matters

Targeting the choroid plexus can enable broad distribution of therapeutic proteins via CSF, making it an attractive strategy for central nervous system gene therapy.

Choroid Plexus

AAV-ChP For Choroid Plexus Targeting ​

AAV-ChP predominantly targets epithelial cells in the choroid plexus, shows minimal transduction of ependymal cells along the CSF barrier, and limits AAV transduction in other brain regions. 

Key Advantages

  • High specificity for ChP epithelial cells vs. control AAVs
  • Minimal ependymal and parenchymal transduction
  • Efficient access via ICV delivery
  • Versatile platform for both basic research and translational studies
AAV-ChP for Choroid Plexus Targeting

Potential Diseases for Choroid Plexus Targeting

1. Lysosomal Storage Disorders (CNS-wide delivery)

  • Examples: MPS I, II, III (Sanfilippo), Batten disease
  • Why ChP: Secretion of therapeutic enzymes into CSF enables broad brain distribution via CSF circulation
  • Advantage: Bypasses limited diffusion from focal injections

2. Neurodegenerative Diseases

  • Examples: Alzheimer’s disease, Parkinson’s disease, ALS
  • Rationale:
    • Modulate CSF composition (e.g., Aβ clearance, neurotrophic factors)
    • Influence neuroinflammation via cytokine signaling
  • Strategy: Continuous secretion of therapeutic proteins into CSF

3. Neuroinflammatory & Autoimmune Disorders

  • Examples: Multiple sclerosis (MS), neuroinflammation syndromes
  • Why ChP matters:
    • Acts as an immune gateway into CNS
    • Can regulate immune cell trafficking and cytokine profiles
  • Opportunity: Reprogram immune signaling locally

4. CNS Infectious Diseases

  • Examples: HIV-associated neurocognitive disorder (HAND), viral encephalitis
  • Approach:
    • Deliver antiviral proteins or immune modulators into CSF
    • Target reservoir or immune interface

5. Hydrocephalus / CSF Dysregulation

  • Examples: Congenital hydrocephalus, CSF overproduction disorders
  • Why ChP:
    • Primary site of CSF production (~70–80%)
  • Strategy: Modulate CSF secretion pathways

6. Brain Tumors (Indirect targeting)

  • Examples: Leptomeningeal metastases, glioblastoma (CSF-disseminated)
  • Concept:
    • Use ChP as a bioreactor to secrete anti-tumor agents into CSF
    • Broad exposure across CNS surfaces

7. Rare Genetic Disorders Affecting CSF or Brain Development

  • Disorders involving:
    • CSF composition imbalance
    • Developmental signaling pathways
  • Potential for early intervention via CSF-mediated delivery