Human galectin 3 binding protein interacts with recombinant adeno-associated virus type 6

Area of Science:

• Gene therapy
• Virology
• Immunology

Background:

• Recombinant adeno-associated viruses (rAAVs) are promising for gene therapy.
• Limited understanding exists regarding rAAV behavior in blood after systemic delivery.

Purpose of the Study:

• To investigate interactions between different rAAV serotypes and serum proteins across species.
• To determine how these interactions affect rAAV biodistribution and transduction efficiency.

Main Methods:

• Screening of serum proteins interacting with various rAAV serotypes in humans, macaques, dogs, and mice.
• Identification of specific protein-vector interactions using serological assays.
• Assessment of the impact of protein binding on rAAV aggregation and transduction in vivo.

Main Results:

• rAAV-1, -5, and -6 serotypes bind to human galectin 3 binding protein (hu-G3BP).
• rAAV-6 exhibits strong binding to G3BP in human and dog sera, but not in macaque or mouse sera.
• In mice, rAAV-6 interacts with C-reactive protein (CRP); hu-G3BP interaction with rAAV-6 causes aggregation and reduced transduction.

Conclusions:

• Species-specific interactions between rAAVs and blood proteins, such as G3BP and CRP, are identified.
• These interactions can lead to vector aggregation and reduced gene transfer efficacy.
• Understanding these protein-vector interactions is crucial for optimizing rAAV delivery and efficacy in different animal models for gene therapy.