Home

Welcome to the AAV-Atlas wiki!

Adeno-Associated Viruses (AAVs) and Their Gene Therapy Applications

Adeno-associated viruses (AAVs) are small, single-stranded DNA viruses belonging to the Parvoviridae family. They are non-pathogenic to humans and depend on co-infection with a helper virus, such as adenovirus or herpesvirus, to replicate. AAVs are characterized by their small genome (~4.7 kb), encapsidated in a non-enveloped icosahedral capsid, and their ability to integrate into the host genome at a specific locus on chromosome 19 in the absence of helper virus, though this integration is rare under therapeutic conditions.

Gene Therapy Applications

AAVs have emerged as one of the most effective and widely used vectors for gene therapy due to several favorable attributes:

1. Non-Pathogenicity: AAVs are inherently non-pathogenic, reducing the risk of adverse effects in therapeutic applications.

2. Tropism Versatility: The ability of AAVs to infect a wide range of cell types, combined with the development of engineered capsid variants, allows for tissue-specific targeting (e.g., liver, muscle, or central nervous system).

3. Long-Term Expression: AAVs are capable of providing long-lasting gene expression in non-dividing cells, making them suitable for treating chronic or genetic conditions.

4. Immune Privilege: AAV vectors elicit relatively mild immune responses compared to other viral vectors like adenoviruses or lentiviruses, which helps avoid immunogenicity-related complications.

Clinical Applications

AAV-based gene therapies have shown success in treating a range of genetic and acquired diseases:

• Inherited Retinal Diseases: Luxturna, the first FDA-approved AAV-based gene therapy, restores vision in patients with biallelic mutations in the RPE65 gene.
• Hemophilia: AAV vectors deliver functional clotting factor genes (e.g., F8 or F9) to patients with hemophilia A or B, enabling reduced dependence on regular factor infusions.
• Neuromuscular Disorders: Zolgensma, an AAV-based therapy, delivers a functional copy of the SMN1 gene to treat spinal muscular atrophy, offering life-saving benefits.
• Liver Disorders: Clinical trials are ongoing for conditions like ornithine transcarbamylase deficiency and glycogen storage diseases using AAVs for liver-targeted gene delivery.

Challenges and Future Directions

Despite their success, AAV-based therapies face several challenges:

• Immunogenicity: Pre-existing antibodies to AAV capsids can limit patient eligibility and therapeutic efficacy.
• Limited Packaging Capacity: AAV's small genome size (~4.7 kb) restricts the size of therapeutic transgenes.
• High Costs: Manufacturing and administering AAV-based therapies remain expensive, limiting accessibility.

Ongoing research focuses on overcoming these hurdles through capsid engineering, development of immunosuppressive strategies, and novel production methods. The rapid expansion of AAV applications underscores their transformative potential in gene therapy.

---