What type of genome does AAV have?
linear single-stranded DNA
AAV has a linear single-stranded DNA (ssDNA) genome of approximately 4.7-kilobases (kb), with two 145 nucleotide-long inverted terminal repeats (ITR) at the termini. The virus does not encode a polymerase and therefore relies on cellular polymerases for genome replication.
How does AAV integrate into the genome?
AAV vectors can integrate by homologous recombination, which is termed AAV-mediated gene targeting . In order to promote homologous recombination, a vector that contains homology arms derived from genomic chromosomal DNA that flank the genetic modification being introduced is used.
What does AAV mean in gene therapy?
Adeno-associated virus (AAV) vectors are the leading platform for gene delivery for the treatment of a variety of human diseases.
What is meant by AAV?
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus Dependoparvovirus, which in turn belongs to the family Parvoviridae.
Is AAV genome circular?
Circular intermediate forms of AAV have been previously proposed, based on the structure of integrated proviruses, as head-to-tail monomer and multimer genomes (3, 5, 18). Circular structures may play roles either as preintegration intermediates or as stable episomal forms resistant to nuclease digestion.
How are AAV vectors made?
AAV viral vectors are produced from packaging cell lines following transfection of the AAV construct and the co-infection with a helper virus, such as adenovirus (Ad) or Herpes Simplex Virus (HSV) or via a single infection with a recombinant helper viral vector containing the rAAV genome.
How does AAV gene delivery work?
How does AAV work? Simply put, AAV is transformed from a naturally occurring virus into a delivery mechanism for gene therapy. The viral DNA is replaced with new DNA, and it becomes a precisely coded vector and is no longer considered a virus, as most of the viral components have been replaced.
Why are AAV vectors used?
Adeno-associated virus (AAV) vectors have been frequently used for gene therapy applications due to the lack of pathogenicity and toxicity, ability to infect both dividing and non-dividing cells, and long-term transgene expression profiles.
Is AAV single-stranded?
Adeno-associated virus (AAV) vectors package single-stranded genomes and require host-cell synthesis of the complementary strand for transduction. However, when the genome is half wild-type size, AAV can package either two copies, or dimeric inverted repeat DNA molecules.
What is the AAV genome?
These features make AAV a very attractive candidate for creating viral vectors for gene therapy, and for the creation of isogenic human disease models. The AAV genome is built of single-stranded deoxyribonucleic acid (ssDNA), either positive- or negative-sensed, which is about 4.7 kilobase long.
How many nucleotides are in AAV?
A: A cartoon showing simulated AAV size and 3-D structure; B: A picture showing electron microscopy of purified AAV vector. The Inverted Terminal Repeat (ITR) sequences comprise 145 nucleotides each.
Where does AAVS1 integrate into the host genome?
As part of its lysogenic cycle, wild-type AAV integrates into the host genome at a specific site, AAVS1 on human chromosome 19. This site is favored due to the presence of a Rep binding element; however, random integrations may occur at a much lower frequency.
What is adeno-associated virus (AAV)?
Adeno-associated virus. Adeno-associated virus ( AAV) is a small virus that infects humans and some other primate species. AAV is not currently known to cause disease. The virus causes a very mild immune response, lending further support to its apparent lack of pathogenicity. In many cases, AAV vectors integrate into the host cell genome,…