Adeno-associated viruses (AAVs) were discovered in the 60s as contaminants of adenoviruses preparations. AAVs are non pathogenic parvoviruses which are found commonly in humans and other animal species. As indicated by the ethymology (parvus = small in latin), parvoviruses are some of the smallest viruses (around 20 nm). AAVs are also known as dependoviruses because they can not replicate and form new viral capsids without the help of another virus such as adeno viruses (hence the name adeno-associated). Therefore AAV replication only happens when an animal is coinfected with both an AAV and an adeno virus.
The genome of AAVs is a linear single-stranded DNA of about 4.7 kb, which is small compared to other types of viruses. Around 120 human and non-human serotypes are known. Due to their low immunogenicity and the fact that the AAV genome tends to integrate in a precise location into the human genome (the AAVS1 site), AAVs are promising vectors for gene therapy.
|AAV serotype||Species of origin|
|2, 3 and 5||humans|
|6||hybrid between AAV 1 and 2|
|7 to 120||isolated from non human primates|
Organisation of the AAV genome
Pseudotyping is the process of producing viral particles incorporating foreign viral envelope proteins. In the case of AAVs, pseudotyping has been used to deliver the same adeno-associated viral DNA (usually from AAV2) to different organs based on the heterogeneous tropism of existing AAV serotypes (a property defined by the capsid proteins).
Nomenclature: a pseudotyped AAV vector containing the ITRs of serotype X encapsidated with the proteins of Y will be designated as AAVX/Y. Example: AAV2/1 has the ITRs of AAV2 and the capsid of AAV1.
Self-complementary AAVs (scAAVs) a.k.a.double-stranded AAVs
The genome of single stranded AAV vector has to be converted to a double-stranded replicative form once it has entered the target cell , which is a rate limiting step in the replicative cycle of AAVs. Double-stranded, self-complementary AAV vectors bypass this step and provide the opportunity to achieve more efficient transduction. The important trade-off for this efficiency is the loss of half the coding capacity of the vector.
- Self-complementary AAV Vectors; Advances and Applications.
- Generation of Novel Double-Stranded AAV Vectors with an Expanded Packaging Capacity Using Linearized 1-AAV ITR DNA Molecules.
- Efficient serotype-dependent release of functional vector into the culture medium during adeno-associated virus manufacturing .
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