Kenneth I. Berns – författare

The Parvoviridae have been of increasing interest to reseachers in the past decade. Their small size and simple structure have made them ame- nable to detailed physiochemical analysis, and from this work relatively detailed information has resulted that has signficantly increased our un- derstanding of the biology of these viruses. It has become clear that the Parvoviridae are of interest not only for their own sake, but also because their relative simplicity renders them useful probes in the study of the biology of host cells and of other DNA viruses with which they interact. The Dependovirus genus, for instance, contains the defective adeno-as- sociated viruses (AA V), which require a coinfection with either an ad- enovirus or a herpesvirus for productive multiplication. Studies of AA V, therefore, necessarily impinge on our understanding of the control of macromolecular synthesis by the helper virus. Similarly AA V has been reported to inhibit the oncogenicity of both adeno-and herpesviruses and has been used as a probe of mechanism in these instances as well.Finally, AA V establishes latent infections in vivo and is the only mammalian DNA virus where a comparable model system has been established in cell culture. This system has allowed study of the mechanism of latent infection at the molecular level.

Human gene therapy holds great promise for the cure of many genetic diseases. In order to achieve such a cure there are two requirements. First, the affected gene must be cloned, its se­ quence determined and its regulation adequately characterized. Second, a suitable vector for the delivery of a good copy of the affected gene must be available. For a vector to be of use several attributes are highly desirable: these include ability to carry the intact gene (although this may be either the genomic or the cDNA form) in a stable form, ability to introduce the gene into the desired cell type, ability to express the introduced gene in an appropriately regulated manner for an extended period of time, and a lack of toxicity for the recipient. Also of concern is the frequency of cell transformation and, in some cases, the ability to introduce the gene into nondividing stem cells. Sev­ eral animal viruses have been tested as potential vectors, but none has proven to have all the desired properties described above. For example, retroviruses are difficult to propagate in sufficient titers, do not integrate into nondividing cells, and are of concern because of their oncogenic properties in some hosts and because they integrate at many sites in the genome and, thus, are potentially insertional mutagens. Additionally, genes introduced by retroviral vectors are frequently expressed for relatively short periods of time. A second virus used as a vector in model systems has been adenovirus (Ad).

Human gene therapy holds great promise for the cure of many genetic diseases. In order to achieve such a cure there are two requirements. First, the affected gene must be cloned, its se­ quence determined and its regulation adequately characterized. Second, a suitable vector for the delivery of a good copy of the affected gene must be available. For a vector to be of use several attributes are highly desirable: these include ability to carry the intact gene (although this may be either the genomic or the cDNA form) in a stable form, ability to introduce the gene into the desired cell type, ability to express the introduced gene in an appropriately regulated manner for an extended period of time, and a lack of toxicity for the recipient. Also of concern is the frequency of cell transformation and, in some cases, the ability to introduce the gene into nondividing stem cells. Sev­ eral animal viruses have been tested as potential vectors, but none has proven to have all the desired properties described above. For example, retroviruses are difficult to propagate in sufficient titers, do not integrate into nondividing cells, and are of concern because of their oncogenic properties in some hosts and because they integrate at many sites in the genome and, thus, are potentially insertional mutagens. Additionally, genes introduced by retroviral vectors are frequently expressed for relatively short periods of time. A second virus used as a vector in model systems has been adenovirus (Ad).