Adenovirus as a gene therapy vector for hematopoietic cells

Adenovirus (Adv)-mediated gene transfer has recently gained new attention a s a means to deliver genes for hematopoietic stem cell (HSC) or progenitor cell gene therapy. In the past, HSCs have been regarded as poor Adv targets , mainly because they lack the specific Adv receptors required for efficien t and productive Adv infection. In addition, the nonintegrating nature of A dv has prevented its application to HSC and bone marrow transduction protoc ols where long-term expression is required. There is even controversy as to whether Adv can infect hematopoietic cells at all. In fact, the ability of Adv to infect epithelium-based targets and its inability to effectively tr ansfect HSCs have been used in the development of eradication schemes that use Adv to preferentially infect and "purge" tumor cell-contaminating HSC g rafts. However, there are data supporting the existence of productive Adv i nfections into HSCs. Such protocols involve the application of cytokine mix tures, high multiplicities of infection, long incubation periods, and more recently, immunological and genetic modifications to Adv itself to enable i t to efficiently transfer genes into HSCs. This is a rapidly growing field, both in terms of techniques and applications. This review examines the two sides of the Adv/CD34 controversy as well as the current developments in t his field.