What is the Difference Between AAV and Lentivirus?

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Adeno-associated virus (AAV) and lentivirus are both widely used for gene transfer, with advantages and disadvantages depending on the application. The main differences between AAV and lentivirus are:

  1. GENOME: AAV has a single-stranded DNA genome, while lentivirus has a single-stranded RNA genome.
  2. ORIGIN: AAV is not derived from a pathogen, but rather is a contaminant of adenovirus. It has no pathogenic conditions associated with it. Lentiviral vectors are derived from the single-stranded RNA retrovirus HIV-1.
  3. INTEGRATION: Both AAV and lentivirus can integrate into the host genome, but they do so at different sites. AAV integrates only at the AAVS1 locus on chromosome 19, also known as the "Safe Harbor" site, where it is commonly used for transgene insertion without harming cells. Lentivirus can integrate at various sites, which may cause non-specific and adverse effects or insertional mutagenesis.
  4. TRANSDUCTION EFFICIENCY: AAV is smaller than lentivirus, giving it an advantage in spreading efficiency within certain tissues. However, lentiviral vectors are VSV-G pseudotyped, allowing them to efficiently transduce any cell from any species.
  5. APPLICATIONS: AAV vectors are highly safe and have been used extensively for in vitro, ex vivo, and in vivo research. Lentiviral vectors are predominantly used for cell therapy applications due to the risk of oncogenes occurring through insertional mutagenesis. However, lentiviral vectors can target specific cell populations without affecting other cells in the same tissue, making them suitable for certain applications.

Choosing between AAV and lentivirus depends on factors such as the specific application, the desired cell type, and the preferred promoter for the cells of interest.

Comparative Table: AAV vs Lentivirus

Adeno-associated virus (AAV) and lentivirus are both widely used for gene delivery in research and therapeutic applications. They have distinct differences, which are summarized in the table below:

Feature AAV Lentivirus
Origin AAV is a non-pathogenic parvovirus that naturally exists in humans and some animals. Lentivirus is derived from HIV and has been highly modified for safety.
Genome Integration AAV does not integrate into the host genome, but remains as episomal DNA. Lentivirus integrates into the host genome, providing stable expression in both dividing and non-dividing cells.
Tropism AAV has a broad tropism, meaning it can infect various cell types. Lentivirus has a limited tropism, but can be pseudotyped with other envelope proteins to broaden its tropism.
Gene Expression AAV mediates long-term, stable gene expression, but at lower levels compared to lentivirus. Lentivirus mediates long-term, stable gene expression at high levels.
Production AAV production is relatively simpler and more cost-effective compared to lentivirus production. Lentivirus production is more complex and expensive.
Safety AAV is considered safer due to its non-pathogenic nature and lack of integration into the host genome. Lentivirus has a higher safety risk due to its HIV origin and genome integration.

Both AAV and lentivirus have their advantages and disadvantages, depending on the specific application. AAV is generally considered safer and more cost-effective, while lentivirus offers higher gene expression levels and stability.