Transcriptomic Profiling Reveals Divergent Immune Responses to AAV1 and AAV-ie in Mice Inner Ear

Area of Science:

• Otorhinolaryngology
• Gene Therapy
• Immunology

Background:

• Adeno-associated virus (AAV) vectors are crucial for gene therapy of hereditary hearing loss.
• AAV transduction in the inner ear can elicit immune responses, including macrophage activation and neutralizing antibody production, potentially limiting therapeutic efficacy.

Purpose of the Study:

• To compare the immune responses induced by different adeno-associated virus (AAV) capsids in the murine cochlea.
• To analyze temporal transcriptomic profiles to understand the dynamics of AAV-induced immune activity.

Main Methods:

• Injected AAV1 and AAV-ie capsids into murine cochleae.
• Analyzed temporal transcriptomic profiles to assess immune responses.

Main Results:

• Both AAV1 and AAV-ie induced immune activity in the cochlea.
• AAV1 elicited significantly later and milder immune reactions compared to AAV-ie.
• Distinct temporal and intensity differences in immune responses were observed between the two capsids.

Conclusions:

• Dynamic cochlear gene expression profiles are critical for understanding AAV immunogenicity.
• Selection of immunologically optimized AAV vectors is essential to minimize adverse immune responses in gene therapy for hereditary hearing loss.