Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65

Area of Science:

• Neuroscience
• Gene Therapy
• Molecular Biology

Background:

• Adeno-associated viral vectors (AAVs) are promising for treating neurologic disorders.
• Crossing the blood-brain barrier (BBB) via intravenous injection enables non-invasive brain delivery.
• Anc80L65 is a novel AAV capsid with demonstrated transduction capabilities in various tissues.

Purpose of the Study:

• To compare the central nervous system (CNS) transduction efficacy of Anc80L65 with AAV9.
• To evaluate Anc80L65 performance after intravenous, intracerebroventricular (i.c.v.), and intraparenchymal injections.
• To assess Anc80L65's potential as a gene transfer vector for the CNS.

Main Methods:

• Intravenous, i.c.v., and intraparenchymal injections of Anc80L65 and AAV9 in a murine model.
• Comparison of transduction efficiency and cell tropism in the brain and spinal cord.
• Analysis of gene expression patterns, including EGFP distribution.

Main Results:

• Anc80L65 demonstrated higher potency than AAV9 for CNS targeting after intravenous injection.
• Anc80L65 transduced astrocytes and diverse neuronal populations.
• Anc80L65 showed more extensive CNS diffusion than AAV9 after i.c.v. infusion, with widespread EGFP expression.

Conclusions:

• Anc80L65 is a highly efficient gene transfer vector for the murine CNS.
• Systemic Anc80L65 injection leads to significant CNS expression without requiring a self-complementary genome.
• Further investigation in larger animal models is warranted.