How Adenovirus and Adeno-Associated Virus Work as Gene Therapy Vectors

Wed, 06/01/2016 - 14:38

Adenoviruses comprise a family of medium sized, non-enveloped viruses that were originally isolated from human adenoids (Rowe et al., 1953). These viruses contain a double stranded DNA genome within an icosahedral nucleocapsid capable of penetrating an endosome without the need for envelope fusion. Researchers using adenovirus antibodies have since identified more than fifty human adenovirus serotypes, which are known to cause a variety of diseases; including upper respiratory tract infections, gastroenteritis, conjunctivitis, and cystitis. Several types have even demonstrated oncogenic potential.

Recombinant adenoviruses have long been seen as useful gene therapy vectors (Heubner et al, 1964), due to their ability to encode proteins without integrating into the host cell genome (Roy-Chowdhury et al., 2002). As adenoviruses infect a host cell, their DNA is not incorporated into the cell's genetic material, but rather remains in a transient extrachromosomal state within the nucleus. The adenovirus DNA is then transcribed just like any other gene, however it is not replicated when the cell undergoes normal division. Additionally, recombinant adenovirus vectors offer the ability to infect both dividing and quiescent cells cells (Zhong et al., 1999).

Adenovirus antibody

Immunohistochemistry analysis of adenovirus antibody clone M58 + M73 (NB120-3648) in human infected appendix tissue.

Adeno-associated virus (AAV) is a small, non-pathogenic satellite virus that is believed to require a helper adenovirus for replication (Atchison et al., 1965). It is similar in structure to adenoviruses, but has a smaller icosahedral nucleocapsid. Researchers soon found that AAV’s structural simplicity and non-pathogenic nature make recombinant AAV (rAAV) a useful gene therapy vector (Gonçalves 2005).

Like adenoviruses, AAV gene therapy vectors can infect both replicating and non-replicating and introduce transgenes without integrating into the genome of the host cell. rAAV vectors are often preferred due to their high titer, ability to infect a broad range of cells, mild immune response, and overall safety. Both recombinant adenoviruses and rAAV gene therapy vectors have been found to highly useful for a number of diseases including diabetes and other pancreatic disorders (Wang et al., 2004). However AAV’s small nucleocapsid (20 nm) limits the genetic material capacity of rAAV vectors, whereas recombinant adenovirus vectors (90–100 nm) can accommodate relatively large transgenes (Gonçalves et al., 2004).

Novus Biologicals offers a range of Adenovirus antibodies and AAV antibodies for use in gene therapy research. For example, the adenovirus antibody (NB600-413) was used to help show how an adenovirus vector carrying the CD40 ligand transgene can inhibit growth of human multiple myeloma cells (Fernandes et al., 2009). Novus also offers a wide range of highly specific antibodies to adenovirus components, including fiber, hexon, and E4 Orf1.


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