Complement inhibition rescued mice allowing observation of transgene expression following intraportal delivery of baculovirus in mice

Abstract

Transgene expression was demonstrated following intraportal infusion of recombinant baculovirus vectors in combination with sCR1; however, our experiments suggest a significant associated toxicity.

Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement

“…Only a single IgM molecule is needed to activate the hemolytic activity of complement, a task that requires roughly 1,000 IgG molecules (11). Natural antibodies and subsequent complement activation cause the lysis or neutralization of many viruses (21,22,38,42,51,52,61). However, we were unable to detect any neutralizing effect of 90% mouse serum on the infectious titer of Ad vectors (our unpublished observations), in agreement with a previous report (2).…”

“…Similar findings have previously been made with a number of other viruses (21,22,37,61). Although the monomeric affinity of natural IgM tends to be much lower than that of affinity-matured antigen-specific IgG antibodies, the avidity of IgM can be very high when bound to repetitive antigens (such as viral capsids), because IgM is a pentamer or a hexamer that contains 10 or 12 Fabs (69).…”

“…Polyreactive natural IgM antibodies play an important role in the control of viral infections in vivo, where they are a vital innate defense during the early stages of an infection, before the adaptive immune system has mounted an antigen-specific response (8,37,38,69). In addition, natural antibodies are a major obstacle to in vivo gene therapy with retroviruses, bacteriophage, herpes simplex virus type 1, and baculovirus (21,42,51,52,61).…”

Expression of hGM-CSF in silk glands of transgenic silkworms using gene targeting vector

“…However, BEVS is a transient expression system and causes the eventual death of worms due to the virus infection. Baculovirus can be transduced into a variety of mammalian cell lines (Hoare et al 2005;Kenoutis et al 2006), and may be potentially harmful. In contrast, transgenic silkworms can easily produce heterologous protein from generation to generation, hence avoiding the full potential harm of the baculovirus infection.…”

Enhanced Baculovirus-Mediated Transduction of Human Cancer Cells by Tumor-Homing Peptides

“…Baculovirus is able to mediate transient and sustained gene delivery to a variety of primary and established cell lines (7, 10, 17-20, 25, 32, 40, 55) as well as to some tissues (21,26,38,39,53). Transgene expression has been demonstrated in vivo with an efficiency comparable to that of adenovirus (1).…”