Terminal glucose as a receptor for adeno-associated virus 44.9

Area of Science:

• Virology
• Gene Therapy Vector Development
• Molecular Biology

Background:

• Novel adeno-associated virus (AAV) serotypes are crucial for advancing gene therapy vectors with unique cell tropism.
• AAV44.9, a natural isolate, shows promise for targeting photoreceptors and salivary glands.
• Understanding AAV tropism and binding is essential for effective gene therapy applications.

Purpose of the Study:

• To elucidate the specific glycan binding requirements of the AAV44.9 vector.
• To identify the molecular determinants of AAV44.9's cell surface interactions.
• To compare AAV44.9's tropism and binding with closely related AAV vectors.

Main Methods:

• Glycan arrays and competition experiments were employed to define AAV44.9's carbohydrate binding preferences.
• Transduction studies confirmed the role of identified glycans in AAV44.9 gene transfer.
• Mutagenesis experiments pinpointed specific capsid amino acids responsible for glycan recognition.

Main Results:

• AAV44.9 specifically binds to terminal glucose on N-linked cell surface carbohydrates.
• This glucose interaction is critical for AAV44.9 vector-mediated transduction.
• Key amino acids involved in AAV44.9's unique glucose binding were identified through comparative analysis with AAVrh.8R.

Conclusions:

• Terminal glucose is a unique glycan receptor for AAV44.9 vectors.
• The identified glycan-binding properties and molecular determinants enhance understanding of AAV tropism.
• This research provides critical insights for optimizing AAV vector design in gene therapy.