10.1.1.1 Viral Vectors

i. Retroviral Vectors

Most of the viral vectors be employed for gene therapy were delivered from retroviruses. The retrovirus life cycle as mentioned before includes converting RNA viral genome into double-stranded DNA, followed by randomly integrates into the host chromosomal DNA. A major disadvantage of these vectors is that they are very labile in the presence of serum complement, which restrict their use to ex vivo protocols. In addition, they have little effects on non-dividing cells.  Also is produced only in relatively low titers.

ii. Adenoviral Vectors

Recombinant adenoviral vectors have been widely employed as vehicles for gene delivery to the lung, because of its attraction to the respiratory tract.  Adenovirus has high efficient gene transfer to a range of cell types in vivo including both dividing and non-dividing.  In addition, they can be concentrated to high titers. One problem for the use of adenoviral vectors for gene therapy is that host cellular immune responses result in transient expression of the delivered therapeutic gene that requires re-administration of the same vector. A second generation of this vector has now been engineered to minimize the expression of viral antigens. Another disadvantage is that the adenoviral genome is not integrated into the host genome so that expression of the therapeutic gene is only transient.

iii. Adeno-Associated Virus

It is non-pathogenic parvovirus with a single stranded DNA genome (Muzyczka, 1992).  It is tropic to the airway epithelium. Its main advantage in gene therapy for the lung diseases is that its ability to integrate with the host genome and affects a variety of cell types including both dividing and non-dividing.  However, its disadvantages are that it is produced in low titer and it can accommodate small size of DNA, which is limited to 4.5 kb.