Advances in gene transfer into haematopoietic stem cells by adenoviral vectors

Until recently, the cells of haematopoietic origin were not considered good adenoviral (Adv) targets, primarily because they lacked the specific Adv receptors required for productive and efficient Adv infections. In addition, because of limitations inherent in Adv infections, such as short-term expression and a non-integrating nature, their application has been precluded from haematopoietic stem cell (HSC) and bone marrow transduction protocols where long-term expression has been required. Therefore, limited research utilising Adv-mediated gene transfer into haematopoietic cells had been conducted. With recent insights into the critical interactions between adenovirus (Adv) and cells, new Adv-mediated gene transduction strategies have now been reported that may overcome these limitations. These new strategies include Adv possessing synthetic polymer coatings, genetically modified capsid proteins or antibody-redirected fibres that can efficiently redirect and retarget Adv to transfer genes into HSC. Additionally, new hybrid Advs, engineered with both modified capsid proteins and novel cis-acting integration sequences, are also being developed which can efficiently deliver and integrate Adv delivered genes into HSC. This is an area of research that is now rapidly gaining momentum in terms of techniques and applications. Here we review the current status of adenovirus-based vectors as a means to achieve high-level gene transfer into haematopoietic cell types.