Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics

Kay, Mark A.; Glorioso, Joseph C.; Naldini, Luigi

doi:10.1038/83324

Cited by 1,169 publications

(789 citation statements)

References 112 publications

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“…Viral vector transduction, however, is actually an abortive infection of the target tissue. Viral vectors, and particularly adenovirus vectors, induce potent host inflammatory and immune responses that limit gene expression and generate significant tissue damage or morbidity (30,31). The events involved in virus entry into a cell activate a number of second messenger pathways and signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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Transplantation of allogeneic grafts presents several challenges to the innate and adaptive immune systems including chemokine leukocyte recruitment, activation, and effector function. We defined the chemokines and receptors induced by the transplant procedure/ischemia injury, alloantigen and gene transfer vector administration in murine cardiac grafts. E1, E3 deleted AdRSVbgal was transferred into grafts at the time of transplantation, grafts were harvested after 1-14 days, and a pathway-specific cDNA array was used to evaluate the levels of 67 chemokine and chemokine receptor genes. Transplantation resulted in ischemic injury and induction of a number of similar genes in both the syngeneic and allogeneic grafts, such as CXCL1 and CXCL5, which increased dramatically on day 1 and returned rapidly to baseline in the syngeneic grafts. Alloantigen stimulated the adaptive immune response and induced the presence of more inflammatory genes within the grafts, particularly at later time points. The adenovirus vector induced a broader panel of genes, among them potent inflammatory chemokines CXCL9 and CXCL10, that are induced earlier or more strongly compared with alloantigen stimulation alone. As alloantigen and adenovirus vectors both induce similar sets of genes, targeting these molecules may not only inhibit alloimmunity, but also enhance the utility of the gene transfer vector.

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Section: Discussionmentioning

confidence: 99%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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“…Adeno-associated viruses, lentiviral vectors and gutless adenoviral vectors may be used for this purpose. [7][8][9] First generation adenoviral vectors are devoid of E1 and E3 viral genes. 10 -12 Cells transduced by this type of vectors express the transgene but also viral proteins.…”

mentioning

confidence: 99%

Prolonged and inducible transgene expression in the liver using gutless adenovirus: A potential therapy for liver cancer

et al. 2004

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“…First, they can provide efficient in vivo gene transfer in both dividing and nondividing cells. 1,2 Secondly, they possess high in vivo stability and can be produced in high titers. Thirdly and most importantly, Ad vectors are not oncogenic or integrated into the human genome and their pathology is mostly limited to mild upper respiratory tract infections.…”

mentioning

confidence: 99%

Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways

et al. 2004

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In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 cell line with the Ad5luc1, a vector which primarily exploits the coxsackie and adenovirus receptor, as its primary native receptor. We found significant changes in gene expression of 5492 genes induced by Ad5luc1 infection, 2439 genes induced by Ad5/3luc1 infection, and 1251 genes induced by Ad5lucRGD infection, compared to unifected cells. Among these changes in gene expression, 783 changes were common to Ad5/3luc1 and Ad5luc1 infections, 266 were common to Ad5lucRGD and Ad5luc1 infections, and 185 changes in gene expression were common to Ad5/3luc1 and Ad5lucRGD infections. Interestingly, 89 changes in gene expression were common to all the three groups, suggesting a commonly affected pathway. This analysis represents a unique application of microarray to study vector-related issues.Furthermore, these studies demonstrate the utility of microarray for characterizing the biologic sequelae of host-vector interaction.

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Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics

Cited by 1,169 publications

References 112 publications

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Prolonged and inducible transgene expression in the liver using gutless adenovirus: A potential therapy for liver cancer

Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways

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