Envelope-targeted retrovirus vectors transduce melanoma xenografts but not spleen or liver.

Many cancer gene therapy applications would benefit from the development of targeted vectors that could deliver genes in vivo. We have previously achieved efficient in vitro targeting of retrovirus vectors to melanoma cells by fusion of a single chain antibody recognizing the high-molecular-weight melanoma-associated antigen (HMWMAA), followed by a blocking peptide and a matrix metalloprotease cleavage site, to the amino terminus of the murine leukemia virus amphotropic strain envelope. Here we report that up to 3% of cells within an HMWMAA-positive tumor xenograft were infected following a single injection of targeted vector into the tumor and up to 10% of tumor cells became infected when they were co-injected with viral producer cells.

Comparison of bicistronic retroviral vectors containing internal ribosome entry sites (IRES) using expression of human interleukin-12 (IL-12) as a readout.

Background: Many gene therapy applications require the co-ordinated delivery of more than one reading frame. We wished to systematically compare IRES in the context of a retroviral vector to determine which was the most effective for protein production and viral titre. To do this we monitored expression of IL-12, as co-ordinated expression of both p35 and p40 subunits is required for production of the active heterodimer.

Synthesis and characterization of histidine-phosphorylated peptides.

Posttranslational phosphorylation of proteins is an important event in many cellular processes. Whereas phosphoesters of serine, threonine, and tyrosine have been studied extensively, only limited information is available for other amino acids modified by a phosphate group. The formation of phosphohistidine residues in proteins was discovered originally in prokaryotic organisms, but also has been found recently in eukaryotic cells.