Adeno-Associated Viruses

Definition

Adeno-associated viruses (AAVs) are small, non-enveloped, single-stranded DNA viruses that belong to the Dependovirus genus. They are considered helper-dependent, as they require the presence of a helper virus, such as an adenovirus or herpes virus, to complete their replication cycle.

5 Must Know Facts For Your Next Test

1. AAVs are considered non-pathogenic and do not cause any known human diseases, making them attractive candidates for gene therapy applications.
2. Recombinant AAVs can be engineered to carry and deliver therapeutic genes to target cells, without the risk of viral replication or integration into the host genome.
3. Different AAV serotypes exhibit varying tropisms, allowing for the selection of the most appropriate serotype for targeting specific cell types or tissues.
4. AAVs can persist in the host cell nucleus as stable, non-integrating episomes, providing long-term gene expression without the risk of insertional mutagenesis.
5. The small packaging capacity of AAVs (approximately 4.7 kb) limits the size of the genetic cargo that can be delivered, but this can be overcome by using strategies such as split-vector systems.

Review Questions

• Explain the role of adeno-associated viruses in gene therapy and their advantages over other viral vectors.
  • Adeno-associated viruses (AAVs) are widely used as gene therapy vectors due to their non-pathogenic nature, ability to deliver genetic material to target cells without integrating into the host genome, and potential for long-term gene expression. Compared to other viral vectors, AAVs offer several advantages, including their low immunogenicity, broad tissue tropism, and the availability of diverse serotypes that can be selected to target specific cell types. The non-integrating nature of recombinant AAVs also minimizes the risk of insertional mutagenesis, making them a safer option for gene therapy applications.
• Describe the dependence of adeno-associated viruses on helper viruses and how this relationship is exploited in gene therapy.
  • Adeno-associated viruses (AAVs) are considered helper-dependent, meaning they require the presence of a helper virus, such as an adenovirus or herpes virus, to complete their replication cycle. This dependency is leveraged in gene therapy applications, where recombinant AAVs are engineered to remove their viral genes and instead carry the therapeutic genetic cargo. The helper virus provides the necessary factors for the recombinant AAV to enter the target cells, traffic to the nucleus, and facilitate the expression of the delivered genes, without the risk of viral replication or integration into the host genome. By separating the AAV from its helper virus, researchers can harness the gene delivery capabilities of AAVs while minimizing the potential for adverse effects.
• Analyze the significance of AAV serotypes and their unique tropisms in the context of targeted gene therapy.
  • The diverse serotypes of adeno-associated viruses (AAVs) are a critical factor in the development of targeted gene therapy. Each AAV serotype is characterized by distinct capsid proteins, which determine the virus's ability to recognize and infect specific cell types or tissues. This property, known as tropism, allows researchers to select the most appropriate AAV serotype for delivering therapeutic genes to the desired target. By matching the AAV serotype to the target cell or tissue, gene therapy can be optimized for improved transduction efficiency and specificity, enhancing the effectiveness and safety of the treatment. The availability of a wide range of AAV serotypes, each with unique tropisms, enables the design of gene therapy approaches tailored to specific disease targets and patient populations.

Related terms

Recombinant AAV: Genetically engineered AAVs that have been modified to remove their viral genes, allowing them to be used as gene therapy vectors for the delivery of therapeutic genetic material.

Serotype: The distinct antigenic properties of different AAV variants, which are classified into different serotypes based on their capsid proteins.

Tropism: The specific target cell types or tissues that a particular AAV serotype can efficiently infect and deliver genetic material to.