Aav-based gene delivery platform for targeted immunomodulatory cytokine production in the brain

Overview

Aila Biotech has developed a proprietary AAV-based gene delivery platform that produces immune-regulating biologics directly at the site of disease within the brain. The platform addresses a critical barrier in neuroimmunology: the inability of most drugs to cross the blood-brain barrier. By using engineered AAV vectors to drive astrocytic production of anti-inflammatory cytokines, the technology enables localized, controlled therapy for neuroinflammatory conditions including multiple sclerosis, traumatic brain injury, stroke, and age-associated cognitive decline.

The platform incorporates a dose-responsive small molecule switch (minocycline-controlled Tet repressor system) that allows precise temporal and spatial control over biologic expression, reducing peripheral off-target toxicities common with systemic delivery. This work is advancing toward first-in-human clinical trials, with the goal of transforming treatment for patients with chronic neuroinflammatory diseases where traditional systemic therapies are limited by toxicity or poor central nervous system penetration.

Technical specifications

Core technology features:

• AAV-based delivery system targeting astrocytes for localized production of anti-inflammatory cytokines, including IL2
• Engineered AAV9 capsid variants with enhanced blood-brain barrier crossing, developed through massively parallel capsid screening in non-human primates (library of 10^6-10^8 unique 7mer insertions at the Q588 loop)
• Minocycline-controlled expression switch enabling small molecule-mediated temporal control over cytokine production
• Optimized DNA cargo design to suppress off-target production and enhance delivery specificity
• Reduced liver and eye off-target entry through capsid evolution and secondary screening validation

Validated applications and results:

• Increased regulatory T cell (Treg) numbers in murine and human brain tissue
• Protection against experimental autoimmune encephalomyelitis (EAE), with reduced clinical severity
• Reduced pathology in traumatic brain injury models (confirmed by histology, MRI, and behavioral testing)
• Protection in stroke models (dMCAO and photothrombotic)
• Mitigation of cognitive decline in ageing models
• Ten-fold expansion of brain Treg numbers in non-human primate studies

Technology readiness level

The platform has been validated across multiple preclinical models, including extensive mouse studies (n>50 for core endpoints) and preliminary non-human primate data demonstrating Treg expansion. Current development focuses on optimizing the AAV capsid and DNA cargo for enhanced primate brain entry and reduced off-target effects. The current clinical development pipeline builds upon the AAV9 capsid, which is already in clinical use for brain-directed gene therapy. The company is advancing its flagship product toward first-in-human clinical trials while continuing to develop additional high-value biologics using the proprietary delivery system. The one-year optimization program will generate improved intellectual property protections and reduce production costs for the therapeutic vector.