Reticuloendotheliosis viruses and derived vectors for human gene therapy

Abstract

The reticuloendotheliosis viruses (REV) spleen necrosis virus (SNV) and reticuloendotheliosis virus strain-A (REV-A) are amphotropic retroviruses which infect a large variety of cells of avian and some mammalian species. They normally do not infect primate or rodent cells. However, they efficiently infect and integrate their genome into that of human cells when they are pseudotyped with the envelope protein of other mammalian retroviruses or the G protein of vesicular stomatitis virus (VSV) or rabies viruses (RV). Moreover, SNV-derived retroviral vectors, which display single chain antibodies or other targeting ligands on the viral surface enable cell-type-specific gene delivery into various human cells. My laboratory has developed genetically engineered REV vectors, which are capable of infecting non-dividing cells such as quiescent human T-cells, primary monocyte-derived macrophages, and mature neurons. Thus, REV-derived vectors appear to be very interesting candidates for the further development of vectors for human gene therapy. This article reviews the replication of REVs and vectors derived from REV-A and SNV for gene transfer into human cells.

The history and principles of retroviral vectors

“…One system has been derived from the closely related avian reticuloendotheliosis viruses strain A (REV-A) and spleen necrosis virus (SNV) (5), the other from ecotropic murine leukemia virus (eco-MLV) (6). REVs and MLV are C-type retroviruses which, like all Ctype retroviruses, express the inner core proteins (gag-pol) from full-length viral RNA and the envelope protein from a spliced RNA (as outlined in Figure 1) (26,30). The first packaging systems closely mimicked a natural retroviral gene transfer system: It consisted of cells, which contained a retrovirus provirus and a retroviral genome carrying a gene of interest.…”

Retroviral packaging cells encapsulated in theracyte immunoisolation devices enable long-term in vivo gene delivery

“…Thus, all experiments had to be terminated about 8 to 10 weeks after the injection of the tumor cells in order not to distress the animals. The use of D17 cells as target had the following advantages: SNVderived vectors infect D17 cells with very high efficiency in vitro (5). Moreover, we have shown previously that D17 cells are also infected in vivo, when they were injected into the peritoneum of SCID mice followed by the injection of vector virus solutions (18).…”

“…Both methods pose a number of problems and limitations. Injections of genetic material such as virus-derived vectors or naked DNA lack control of the therapeutics introduced into the patient with limited guarantee that the target will be reached (4,5). Moreover, direct injections of naked DNA and certain viral constructs such as adenovirus-derived vectors into the tissue produce only transient expression, and, therefore, are short-lived (6).…”

“…The pore size of the device is large enough to release retroviral vectors. not infectious in human or rodent cells (5,12,13). However, SNV-derived retroviral vectors efficiently infect human cells, when they are endowed with a targeting envelope, e.g., single chain antibodies (14)(15)(16)(17)(18)(19)(20), or when pseudotyped with the envelope of other viruses including vesicular stomatitis virus (VSV) or rabies viruses (Parveen et al, submitted).…”

Characterization of an alternative packaging system derived from the cat RD114 retrovirus for gene delivery

“…The four other most advanced retroviral systems are derived from the avian reticuloendotheliosis virus, from the avian sarcoma and leukosis viruses (ASLVs), from the foamy virus and from the lentivirus 16–19. The latest two are considered ‘complex’ retroviruses because, in addition to Gag‐pol and Env, they encode small regulatory proteins.…”