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Retroviral targeting of proliferating endothelial cells

100%

Gornikiewicz A., Zommer A., Jakesz R., Gnant M., Brostjan C.

2005

vol. 52

issue 3

731-735

Tumor growth requires the formation of new blood vessels by endothelial cells. Thus, surface molecules - such as angiogenin receptors - that are selectively expressed on growing endothelium represent an attractive target for directed delivery of compounds to tumor tissue. We attempted to obtain genetically engineered retroviral vectors targeted to the endothelium by inserting the human angiogenin sequence into Moloney murine leukemia virus envelope glycoprotein. Abundant expression of the chimeric protein could be verified. However, while being selective for proliferating human endothelial cells, the recombinant retroviral particles displayed low transduction efficiencies and thus have to be further improved.

Low recombination activity of R region located at both ends of the HIV-1 genome

86%

Urbanowicz A., Kurzyńska-Kokorniak A., Jankowska A., Alejska M., Figlerowicz M.

2012

vol. 59

issue 4

619-626

Although two strand transfer events are indispensable for the synthesis of double-stranded DNA and establishing HIV-1 infection, the molecular basis of these phenomena is still unclear. The first obligatory template switching event occurs just at the beginning of the virus replication cycle and involves two copies of the 97-nucleotide long R region, located one each at the both ends of the HIV-1 genome (HIV-1 R). Thus, one can expect that the molecular mechanism of this process is similar to the mechanism of homologous recombination which operates in RNA viruses. To verify the above-mentioned hypothesis, we attempted to assess the recombination activity of HIV-1 R. To this end, we tested in vitro, how effectively it induces template switching by HIV-1 RT in comparison with another well-characterized sequence supporting frequent homologous crossovers in an unrelated virus (R region derived from Brome mosaic virus - BMV R). We also examined if the RNA sequences neighboring HIV-1 R influence its recombination activity. Finally, we tested if HIV-1 R could cause BMV polymerase complex to switch between RNA templates in vivo. Overall, our results have revealed a relatively low recombination activity of HIV-1 R as compared to BMV R. This observation suggests that different factors modulate the efficiency of the first obligatory strand transfer in HIV-1 and the homology-driven recombination in RNA viruses.

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2 Acta Biochimica Polonica

1 2012

1 2005

1 Alejska M.

1 Brostjan C.

1 Figlerowicz M.

1 Gnant M.

1 Gornikiewicz A.

1 Jakesz R.

1 Jankowska A.

1 Kurzyńska-Kokorniak A.

1 Urbanowicz A.

1 Zommer A.

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Retroviral targeting of proliferating endothelial cells

Low recombination activity of R region located at both ends of the HIV-1 genome