Virus Vectors for use in the Central Nervous System

Adeno-Associated Viral (AAV) vectors play a key role in preclinical gene therapy studies for a number of diseases, including diseases of the brain. AAVs have many appealing characteristics that make its recombinant derivatives very attractive tools for human gene therapy. AAV is classified as a member of the mammalian Parvovirus family, which is among the smallest and structurally simplest of the DNA viruses. The Parvovirus family has been divided into three genera: parvovirus, densovirus, and dependovirus. AAVs constitute the latter genus, so called because of the requirement for a helper virus coinfection to enable productive infection to occur. Adeno-associated viruses specific for species ranging from chicken to human have been isolated. A total of eight different serotypes of AAV (AAV1–8) has been isolated to date of which the serotype 2 is the most characterized as its infectious clone was the first one made. Although AAV is known to have a very broad host range, there are striking differences in in vivo transduction efficiency of rAAV vectors in various tissues and cells. The inability of the vector to enter specific cells due to a lack of its receptors that mediate virus binding and entry is a limiting step for efficient gene delivery.