Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice

Smith, Theodore A; Mehaffey, Michele G.; Kayda, Dawn B.; Saunders, June M.; Yei, Soonpin; Trapnell, Bruce C.; McClelland, Alan; Kaleko, Michael

doi:10.1038/ng1293-397

Cited by 344 publications

(211 citation statements)

References 28 publications

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“…administration. 54 The marked increase in copy number and E1A and E4 expression in the liver at the high dose was correlated with changes in toxicological end points such as an early transient decrease in platelet counts and an elevation in serum liver enzymes (Fig 6b, Table 3). At the high dose, there appears to be a loss of gene regulation and unrestricted viral DNA replication in liver.…”

Section: Discussionmentioning

confidence: 83%

Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer

et al. 2004

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A potentially promising treatment of metastatic cancer is the systemic delivery of oncolytic adenoviruses. This requires engineering viruses which selectively replicate in tumors. We have constructed such an oncolytic adenovirus, OAS403, in which two early region genes are under the control of tumor-selective promoters that play a role in two key pathways involved in tumorigenesis. The early region E1A is controlled by the promoter for the E2F-1 gene, a transcription factor that primarily upregulates genes for cell growth. The E4 region is under control of the promoter for human telomerase reverse transcriptase, a gene upregulated in most cancer cells. OAS403 was evaluated in vitro on a panel of human cells and found to elicit tumor-selective cell killing. Also, OAS403 was less toxic in human hepatocyte cultures, as well as in vivo when compared to an oncolytic virus that lacked selective E4 control. A single intravenous injection of 3 Â 10 12 vp/kg in a Hep3B xenograft mouse tumor model led to significant antitumor efficacy. Additionally, systemic administration in a pre-established LNCaP prostate tumor model resulted in over 80% complete tumor regressions at a tolerable dose. Vector genome copy number was measured in tumors and livers at various times following tail vein injection and showed a selective time-dependent increase in tumors but not livers over 29 days. Furthermore, efficacy was significantly improved when OAS403 treatment was combined with doxorubicin. This virus holds promise for the treatment of a broad range of human cancers including metastatic disease.

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Section: Discussionmentioning

confidence: 83%

Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer

et al. 2004

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“…K562 cells were transduced with Av9 RSVLacZ4, a vector with adenovirus 3 receptor binding speci- ficity, 29 and Av1 RSV-LacZ4, a vector with adenovirus 5 receptor binding specificity. 30 Av9 RSV-LacZ4 differs from Av1 RSV-LacZ4 in that it (Av9 RSV-LacZ4) contains a chimeric fiber gene in which the sequences encoding the fiber head have been replaced with corresponding sequences from an adenovirus 3 serotype virus. Av1 RSV-LacZ4 has the conventional fiber gene encoding a protein of adenovirus 5 serotype.…”

Section: Resultsmentioning

confidence: 99%

“…The plasmid pAd-CMV-EcoRec was made by a three-way ligation between the 3.1 kb SalI-StuI from pCMV-EcoRec, and the 3.6 kb XhoI-EcoRI and the 5. Recombination between pAVs6-EcoRec and Av1 RSVLacZ4 30 or Av9 RSV-LacZ4 29 in 293 cells resulted in the formation of Av1 RSV-EcoRec or Av9 RSV-EcoRec, respectively. Similarly recombination between pAd-CMV-EcoRec and Av1 RSV-LacZ4 30 or Av9 RSV-LacZ4 29 resulted in the formation of Av1 CMV-EcoRec or Av9 CMV-EcoRec, respectively.…”

Section: Generation Of Recombinant Adenoviral Viral Vectors Encoding mentioning

confidence: 99%

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

et al. 1999

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One factor limiting the ability to modify human repopulating to 48%) by replacing the RSV promoter with the CMV E1a hematopoietic cells genetically with retroviral vectors is the promoter, resulting in a parallel increase in retroviral transrelatively low expression of the cognate viral receptor. We duction efficiency. Replacing the head portion of the fiber have tested sequential transduction of human hematopoprotein in conventional adenoviral vectors (serotype 5) with ietic cells with an adenoviral vector encoding the ecotropic the corresponding portion from an adenoviral 3 serotype retroviral receptor followed by transduction with an ecoresulted in ecotropic receptor expression in 60% of CD34 + tropic retroviral vector. Adenoviral transduction of K562 cells at an MOI of 10 4 and a retroviral transduction of 60% erythroleukemia cells was highly efficiently with Ͼ95% of of hematopoietic clonogenic progenitors. The sequential cells expressing the ecotropic receptor at a multiplicity of transduction strategy also resulted in efficient transduction infection (MOI) of 10 3 with a correspondingly high transof the primitive CD34 + CD38 − subset suggesting that it may duction with a retroviral vector. Ecotropic receptor hold promise for genetic modification of human hematopoexpression in CD34 + cells following transduction with adenietic stem cells. oviral vectors was increased by at least two-fold (from 20

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“…11 Gene transfer to skeletal muscles has been hampered in part due to the inability of current generation vectors to infect a significant number of cells. [12][13][14][15][16][17][18][19] Although adeno-associated virus (AAV) efficiently infects muscle and elicits sustained gene expression, its capacity for delivering and regulating large genes is limited. As for the large DNA viruses such as HSV and adenovirus, muscle fibers exhibit a maturation-dependent loss of susceptibility to infection.…”

Section: Introductionmentioning

confidence: 99%

Efficient infection of mature skeletal muscle with herpes simplex virus vectors by using dextran sulfate as a co-receptor

1999

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The use of herpes simplex virus (HSV) vectors for gene chondroitin ABC lyase, HSV infection was restored, which delivery to skeletal muscle is hampered by a maturationsuggests that virus secondary receptors were present but dependent loss of muscle fiber infectivity. Previous studies not readily accessible to the virus in the intact myofiber. of HSV type 1 (HSV-1) infection in the rodent show that Surprisingly, we also found that HSV-1 infectivity could be the loss of infectivity may be due, at least in part, to the restored in vitro and in vivo by exposing myofibers to low development of the basal lamina throughout the course of concentrations of the glycosaminoglycan analog dextran maturation, which may block the initial events in HSV infecsulfate, which appears to act as a surrogate receptor to tion. To initiate infection, HSV normally attaches to cell surstabilize the virus at the myofiber surface such that HSV face heparan sulfate, which stabilizes the virus such that can engage additional receptors. This demonstration that it can interact with secondary protein receptors required the basal lamina is not an absolute block to HSV-1 infecfor entry into host cells. In this study, we demonstrate that tion is remarkable because it allows for the nondestructive heparan sulfate biosynthesis is downregulated during skeltargeting of HSV-1 to mature myofibers and greatly etal muscle maturation. When myofibers were treated with expands the usefulness of HSV as a gene therapy vector a variety of enzymes, including collagenase type IV or for the treatment of inherited and acquired diseases.

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Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice

Cited by 344 publications

References 28 publications

Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer

Antitumor efficacy and tumor-selective replication with a single intravenous injection of OAS403, an oncolytic adenovirus dependent on two prevalent alterations in human cancer

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector

Efficient infection of mature skeletal muscle with herpes simplex virus vectors by using dextran sulfate as a co-receptor

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