TY - JOUR
T1 - Advances in gene transfer into haematopoietic stem cells by adenoviral vectors
AU - C Marini, Frank
AU - Shayakhmetov, Dmitry
AU - Gharwan, Helen
AU - Lieber, Andre
AU - Andreeff, Michael
N1 - Funding Information:
The authors would like to thank C Jordan and P Yotnda for helpful discussions and critical review of this manuscript. This work was supported by a grant from The Susan G Komen Breast Cancer Foundation and the WM Keck Center (FCM) and by NIH grants P01 HL53750 and P30 DK 47754 (AL) and a grant from the Cystic Fibrosis Foundation (DMS).
PY - 2002/12
Y1 - 2002/12
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Capsid proteins
KW - Gene therapy
KW - Haematopoietic stem cells
KW - Retargeting
KW - Vector polycation complex
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U2 - 10.1517/14712598.2.8.847
DO - 10.1517/14712598.2.8.847
M3 - Review article
C2 - 12517264
AN - SCOPUS:0036919337
SN - 1471-2598
VL - 2
SP - 847
EP - 856
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 8
ER -