AAV2/9 Enables Superior Germ Cell Transduction in Mouse Testes

Area of Science:

• Gene therapy
• Viral vectors
• Reproductive biology

Background:

• Recombinant adeno-associated virus (rAAV) is crucial for gene therapy, offering safety and sustained expression.
• Hybrid rAAV vectors combine AAV2 genome with diverse capsids for targeted delivery.
• Engineered rAAVs enhance tissue specificity and minimize off-target effects in gene delivery.

Purpose of the Study:

• To identify the optimal hybrid vector for germ cell-directed gene delivery in mice.
• To evaluate the efficacy and safety of different chimeric AAV variants for testicular gene transfer.

Main Methods:

• Generated ten distinct chimeric AAV variants (AAV2 genome with various capsids).
• Administered vectors via microinjection into mouse seminiferous tubules.
• Assessed transduction efficiency and EGFP expression at 4 weeks post-injection.

Main Results:

• AAV2/9 demonstrated robust and widespread enhanced green fluorescent protein (EGFP) expression in the mouse testis.
• Immunofluorescence confirmed AAV2/9 efficiently transduced nearly all testicular cells with durable expression.
• No adverse effects on testicular development or spermatogenesis were observed with AAV2/9.

Conclusions:

• AAV2/9 is a highly effective vector for gene delivery to murine testicular germ cells.
• Its favorable safety profile and high transduction efficiency position AAV2/9 for therapeutic applications.
• AAV2/9 is a premier vector for germ cell-directed gene therapy, informing capsid selection for male infertility treatments.