Principles of Virology, Volume 1. Jane Flint

Principles of Virology, Volume 1 - Jane Flint


Скачать книгу
href="#ulink_4b8b231c-21d3-5498-926a-e8c372576aa2">Table 3.1 Some viral vectors

Virus Insert size Integration Duration of expression Advantages Potential disadvantages
Adeno-associatedvirus ~5 kb No Long Nonpathogenic, episomal, infects nondividing and dividing cells, broad tropism, low immunogenicity Small transgene capacity, helper virus needed for vector production
Adenovirus ~8–38 kb No Short Broad tropism, efficient gene delivery, infects nondividing and dividing cells, large cargo capacity Transient, immunogenic, high levels of preexisting immunity
Baculovirus No known upper limit No Short High levels of protein synthesis, recombinant viruses easily made, more than one protein can be made in same cells Insect cells typically used, no replication in mammalian cells, human type protein glycosylation not 100% efficient, paucimannose structures present
Gammaretroviru s (murine leukemia virus) 8 kb Yes Short Stable integration, broad tropism possible via pseudotyping, low immunogenicity, low preexisting immunity Risk of insertional mutagenesis, poor infection of nondividing cells, faulty reverse transcription
Herpes simplex virus ~50 kb No Long in central nervous system, short elsewhere Infects nondividing cells, large capacity, broad tropism, latency Virulence, persistence in neurons, high levels of preexisting immunity, may recombine with genomes in latently infected cells
Lentivirus 9 kb Yes Long Stable integration, transduces nondividing and dividing cells Potential insertional mutagenesis; none detected in clinical trials
Rhabdovirus ~4.5 kb No Short High-level expression, rapid cell killing, broad tropism, lack of preexisting immunity Virulence, highly cytopathic, neurotropism, immunogenic
Vaccinia virus ~30 kb No Short Wide host range, ease of isolation, large capacity, high-level expression, low preexisting immunity Transient, immunogenic
image

      Vaccinia virus and other animal poxvirus vectors offer the advantages of a wide host range, a genome that accepts very large fragments, high expression of foreign genes, and relative ease of preparation. Foreign DNA is usually inserted into the viral genome by homologous recombination, using an approach similar to that described for marker transfer. Because of the relatively low pathogenicity of the virus, poxvirus recombinants have been considered candidates for human and animal vaccines.

      Baculoviruses, which infect arthropods, have large circular dsDNA genomes. These viruses have been modified to become versatile and powerful vectors for the production of proteins for research and clinical use. The general approach is to replace the viral polyhedron gene with the gene of interest. Recombinant viruses are produced in E. coli using a bacmid vector that harbors the baculovirus genome. The gene to be introduced is inserted into the baculovirus genome by recombination. Strong viral promoters are used to obtain high levels of protein production. Recombinant baculoviruses are obtained after transfection of bacmids into insect cells and have been used for protein production for research purposes and for large-scale synthesis for commercial uses. Examples include the influenza virus vaccine FluBlok, which consists of the viral HA proteins produced in insect cells via a baculovirus vector, and porcine circovirus 2 vaccine for the prevention of fatal disease in swine.

image
Скачать книгу