Improving neuronal transduction with nanobody-displaying AAV vectors

Can AAV retargeting improve gene delivery to neuronal cells?

AAV vectors are widely used for gene delivery, but their ability to transduce neuronal cells remains limited without further adaptation. Capsid engineering through library screening can identify vectors with new properties, but often requires extensive experimental work and animal studies.

Researchers engineered AAV vectors displaying a nanobody within the VP3 capsid domain and evaluated them in human iPSC-derived inhibitory AD2 and excitatory NGN2 neuronal cultures. Different promoters and vector doses were tested across both neuronal subtypes.

Nanobody-displaying vectors achieved transduction rates of 40–65% and improved transduction by up to threefold compared with the best-performing protocols used as positive controls. Nanobody insertion improved performance across the AAVs tested, with no promoter- or capsid-related toxicity observed.

Download the poster to explore:

• Design and manufacturing of nanobody-displaying AAV vectors
• Transduction of iPSC-derived NGN2 and AD2 neuronal cells
• Effects of vector dose on transduction
• Performance across different promoters
• Nanobody-mediated AAV retargeting for neuronal research

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