Abbreviations: IFNγ, interferon gamma; IL-2, interleukin 2; TK, thymidine kinase (sometimes used with bromodeoxyuridine); HSV-TK, herpes
a
simplex thymidine kinase, often coupled with gancyclovir treatment; BRCA-1, breast cancer 1, early onset; PSA, puromycin-sensitive aminopeptidase;
CEA, carcinoembryonic antigen; GM-CSF, granulocyte-macrophage colony stimulating factor; MDR-1, multi-drug resistance protein 1 (used to insert
chemotherapy-resistance genes into the hematopoetic lineage); CD80, protein involved in T-cell activation; CD, cytosine deaminase; TNF, tumor necrosis
factor.
b
Definitions of phases in a clinical trial: Phase I usually fewer than 100 healthy volunteers, primarily to gauge adverse reactions, and to determine optimal
dose and best route of administration. Phase II are generally pilot efficacy studies usually involving 200500 volunteers randomly assigned to control and
study groups. Phase II will test for immunogenicity in the case of vaccines, and duration of expression and amelioration of symptoms for gene therapy. Note
that none of these trials have proceeded beyond Phase II, and most are in Phase I.
Source: Wiley Journal of Gene Medicine/Clinical Trial Database at: http://www.wiley.co.uk/genetherapy/clinical/.
The possible use of herpesviruses to control brain tumors,
Nonviral Vectors for Gene Therapy
especially gliomal tumors, has been cited earlier. Simple ret-
Boulaiz, H., Marchal, J. A., Prados, J., Melguizo, C., and Aránega, A. (2005).
roviruses are also being examined for this purpose. These
Non-viral and viral vectors for gene therapy. Cell. Mol. Biol. 51: 322.
viruses can only replicate in dividing cells. Thus, they
Cohen, E. P., de Zoeten, E. F., and Schatzman, M. (1999). DNA vaccines as
should be able to infect only tumor cells in the brain, since
cancer treatment. American Scientist 87: 328335.
most neuronal cells are terminally differentiated and do not
divide. If the retroviruses express a protein that renders the
Viruses as Vectors for Heterologous
cells sensitive to a toxin, it might be possible to kill replicat-
Antigen Expression
ing cells and therefore only the tumor cells.
Basak, S., McPherson, S., Kang, S., et al. (1998). Construction and
characterization of encapsilated poliovirus replicons that express
FUR THER READING
biologically active murine interleukin-2. J. Interferon Cytokine Res.
18: 305313.
Infectious Clones
Bledsoe, A. W., Jackson, C. A., McPherson, S., et al. (2000). Cytokine pro-
duction in motor neurons by poliovirus replicon vector gene delivery.
Bredenbeek, P. J., Kooi, E. A., Lindenbach, B., et al. (2003). A stable full-
Nature Biotechnol. 18: 964969.
length yellow fever virus cDNA clone and the role of conserved RNA
Bukreyev, A., Skiadopoulos, M. H., Murphy, B. R., and Collins, P. L.
elements in flavivirus replication. J. Gen. Virol. 84: 12611268.
(2006). Nonsegmented negative-strand viruses as vaccine vectors.
Bridgen, A., and Elliott, R. M. (1996). Rescue of a segmented negative-
J. Virol. 80: 1029310306.
strand RNA virus entirely from cloned complementary DNAs. Proc.
de Haan, C. A. M., Haijema, B. J., Boss, D., Heuts, F. W. H., and Rottier,
Natl. Acad. Sci. U.S.A. 93: 1540015404.
P. J. M. (2005). Coronaviruses as vectors: stability of foreign gene
Conzelmann, K.-K., and Meyers, G. (1996). Genetic engineering of animal
expression. J. Virol. 79: 1274212751.
RNA viruses. Trends Microbiol. 4: 386393.
Gillet, L., Daix, V., Donofrio, G., et al. (2005). Development of bovine her-
Domi, A., and Moss, B. (2002). Cloning the vaccinia virus genome as a
pesvirus 4 as an expression vector using bacterial artificial chromosome
bacterial artificial chromosome in Escherichia coli and recovery of
cloning. J. Gen. Virol. 86: 907917.
infectious virus in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 99:
Mackett, M., Smith, G. L., and Moss, B. (1982). Vaccinia virus: a selectable
1241512420.
eukaryotic cloning and expression vector. Proc. Natl. Acad. Sci. U.S.A.
Komoto, S., Sasaki, J., and Taniguchi, K. (2006). Reverse genetics system
79: 74157419.
for introduction of site-specific mutations into the double-stranded
Monath, T. P., Levenbook, I., Soike, K., et al. (2000). Chimeric yellow
RNA genome of infectious rotavirus. Proc. Natl. Acad. Sci. U.S.A. 103:
fever virus 17D-Japanese encephalitis virus vaccine: Dose-response
46464651.
effectiveness and extended safety testing in rhesus monkeys. J. Virol.
Neumann, G., and Kawaoka, Y. (2004). Reverse genetics systems for the
74: 17421751.
generation of segmented negative-sense RNA viruses entirely from
Pennathur, S., Haller, A. A., MacPhail, M., et al. (2003). Evaluation of atten-
cloned DNA. Curr. Top. Microbiol. Immunol. 283: 4360.
uation, immunogenicity and efficacy of a bovine parainfluenza virus
Rice, C. M., Levis, R., Strauss, J. H., and Huang, H. V. (1987). Production of
type 3 (PIV-3) vaccine and a recombinant chimeric bovine/human PIV-3
infectious RNA transcripts from Sindbis virus cDNA clones: Mapping
vaccine vector in rhesus monkeys. J. Gen. Virol. 84: 32533261.
of lethal mutations, rescue of a temperature sensitive marker, and in vitro
Perri, S., Greer, C. E., Thudium, K., et al. (2003). An alphavirus replicon
mutagenesis to generate defined mutants. J. Virol. 61: 38093819.
particle chimera derived from Venezuelan equine encephalitis and
Schnell, M. J., Mebatsion, T., and Conzelmann, K.-K. (1994). Infectious
Sindbis viruses is a potent gene-based vaccine delivery vector. J. Virol.
rabies viruses from cloned cDNA. EMBO J. 13: 41954203.
77: 1039410403.
Shi, P.-Y., Tilgner, M., Lo, M. K., Kent, K. A., and Bernard, K. A. (2002).
Pinto, V. B., Prasad, S., Yewdell, J., et al. (2000). Restricting expression
Infectious cDNA clone of the epidemic West Nile virus from New York
prolongs expression of foreign genes introduced into animals by retro-
City. J. Virol. 76: 58475856.
viruses. J. Virol. 74: 1020210206.
Thumfart, J. O., and Meyers, G. (2002). Feline calicivirus: recovery of wild-
Schneider, U., Bullough, F., Vongpunsawad, S., et al. (2000). Recombinant
type and recombinant viruses after transfection of cRNA or cDNA con-
measles viruses efficiently entering cells through targeted receptors. J.
structs. J. Virol. 76: 63986407.
Virol. 74: 99289936.
Search WWH :
