Perinatal systemic gene delivery using adeno-associated viral vectors

Area of Science:

• Neuroscience
• Genetics
• Pediatrics

Background:

• Neurodegenerative monogenic diseases impact multiple organ systems, necessitating systemic treatment approaches.
• Current therapies struggle to cross the blood-brain barrier (BBB), limiting central nervous system efficacy.
• Early-onset, lethal neurodegenerative diseases require interventions during the perinatal period to prevent irreversible pathology.

Purpose of the Study:

• To review advancements in adeno-associated virus (AAV) vector technology for systemic gene delivery.
• To explore the potential of AAV-mediated perinatal gene therapy for early-lethal neurodegenerative disorders.
• To assess the feasibility of intravenous AAV administration for crossing the BBB and achieving therapeutic effects.

Main Methods:

• Review of scientific literature on AAV serotypes and their ability to cross the BBB.
• Analysis of studies demonstrating safety and efficacy of perinatal AAV administration in preclinical models (mice and non-human primates).
• Evaluation of systemic transduction achieved through intravenous AAV delivery.

Main Results:

• Specific AAV serotypes demonstrate the capacity to cross the BBB after intravenous administration.
• Perinatal administration of AAV vectors has shown safety in both mice and non-human primates.
• Systemic transduction is achievable, offering a potential route for therapeutic intervention.

Conclusions:

• Perinatal gene therapy using AAV vectors is a promising strategy for early-lethal neurodegenerative diseases.
• Intravenous AAV delivery offers a systemic approach to overcome the BBB challenge.
• Further development of AAV-based perinatal gene therapy could revolutionize treatment for devastating childhood neurological disorders.