Skip to main content

Application of Alphavirus Vectors in Drug Discovery

  • Chapter
Animal Cell Technology: From Target to Market

Part of the book series: ESACT Proceedings ((ESACT,volume 1))

  • 33 Accesses

Abstract

Alphavirus vectors have proven useful for various in vitro and in vivo applications. The rapid generation of high-titer recombinant alphavirus particles has resulted in overexpression of topologically different recombinant proteins in a broad range of mammalian host cells. The same replication-deficient alphavirus particles have been subjected to in vivo gene delivery studies. These features have made alphavirus vectors attractive for various approaches in drug discovery. Large-scale production of recombinant G protein-coupled receptors and ligand-gated ion channels has significantly facilitated drug screening procedures and purification of receptor protein for biostructural studies. Modified alphavirus vectors with lower cytotoxicity and a temperature-sensitive phenotype has allowed prolonged survival of host cells and inducible expression studies. Furthermore, vectors have been engineered for functional expression of cDNA libraries and the use of vector for anfisense and ribozyme applications. Preliminary studies in animal models have indicated that alphaviruses are potentially attracdve for gene therapy applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 379.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agapov, E.V., I. Frolov, B.D. Lindenbach, B.M. Pragai, S. Schlesinger, and CM. Rice. “Noncytopathogenic Sindbis RNA vectors for heterologous gene expression”. Proc. Natl. Acad. Sci. USA 95 (1998): 12989–12994.

    Article  PubMed  CAS  Google Scholar 

  • Altman-Hamandzic, S., C. Groceclose, J.-X. Ma, D. Hamandzic, N. S. Vrindavanam, L.D. Middaugh, N.R Paratto, and F.R. Sallee. “Expression of ß-galactosidase in mouse brain: utilization of a novel nonreplicative Sindbis virus vector as a neuronal gene delivery system”. Gene Then 4 (1997): 815–822.

    Article  Google Scholar 

  • Asselin-Paturel, C., N. Lassau, J.-M. Guinebredere, J. Zhang, F Gay, F. Bex, S. Hallez, J. Leclere, P. Peronneau, F. Mami-Choauib, and S. Chouaib. “Transfer of the murine interleukin-12 gene in vivo by a Semliki Forest virus vector induces tumor regerssion through inhibition of tumor blood vessel formadon monitored by Doppler ultrasynography”. Gene Then 6 (1999): 606–615.

    Article  CAS  Google Scholar 

  • Blasey, H.D., K. Lundstrom, S. Tate, and A.R. Bernard. “Recombinant protein production using the Semliki Forest virus expression system”. Cytotechnology 24 (1997): 65–72.

    Article  PubMed  CAS  Google Scholar 

  • Boorsma, M., D. Koller, and M.R Bachmann. “New applications of alphavirus-based expression vectors”. Cytotechnology (2001): in press.

    Google Scholar 

  • Boorsma, M., L. Nieba, D. Koller, M.F. Bachmann, J.E. Bailey, and W.A. Renner. “A temperature-regulated replicon-based DNA expression system”. Nat. Biotech. 18 (2000): 429–432.

    Article  CAS  Google Scholar 

  • Davis, N.L., L.W. Willis, J.F. Smith, and R.E. Johnston. “In vitro synthesis of infectious Venezuelan equine encephahtis virus RNA from a cDNA clone: analysis of a viable deletion mutant”. Virology 171 (1989): 189–204.

    Article  PubMed  CAS  Google Scholar 

  • Ehrengruber, M.U., K. Lundstrom, C. Schweitzer, C. Heuss, S. Schlesinger, and B.H. Gähwiler. “Recombinant Semliki Forest virus and Sindbis virus efficiently infect neurons in hippocampal slice cultures”. Proc. Natl. Acad Sci. USA 96 (1999): 7041–7046.

    Article  PubMed  CAS  Google Scholar 

  • Ehrengruber, M.U., S. Hennou, H. Büeler, H.Y. Naim, N. Déglon, and K. Lundstrom. “Gene transfer into neurons from hippocampal slices: comparison of recombinant Semliki Forest virus, adenovirus, adeno-associated virus, lentivirus, and measles virus”. Mol. Cell. Neurosci. 17 (2001): 855–871.

    Article  PubMed  CAS  Google Scholar 

  • Hovius, R., A.-P. Tain, H. Blasey, A. Bernard, K. Lundstrom, and H. Vogel. “Characterization of a mouse serotonin 5-HT3 receptor purified from mammalian cells”. J. Neurochem. 70 (1998): 824–834.

    Article  PubMed  CAS  Google Scholar 

  • Liljeström, P., and H. Garoff. “A new generation of animal cell expression vectors based on the Semliki Forest virus replicon”. Bio/Technology 9 (1991): 1356–1361.

    Article  PubMed  Google Scholar 

  • Lundstrom, K. “Alphavirus vectors as tools in neurobiology and gene therapy”. J. Receptor & Signal Transd. Res. 19 (1999): 673–686.

    Article  CAS  Google Scholar 

  • Lundstrom, K. “Alphavirus vectors: applications for DNA vaccine and gene expression”. Intervirology 43 (2000): 247–257.

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom. K., A.B. Hawcock, A. Vargas, P. Ward, P. Thomas, and A. Naylor. “Effect of single point mutations of the human tachykinin NKl receptor on antagonist activity”. Eun J. Pharmacol. 337 (1997a): 73–81.

    Article  CAS  Google Scholar 

  • Lundstrom, K., F. Knoflach, F. Goepfert, H. Schaffhauser, J.R. Pink, Y. Borer, P Ziltener, and V. Mutel. “Functional expression of metabotropic glutamate receptors in primary neurons infected with Semliki Forest virus vectors”. J. Neurochem. 73Suppl. 1 (1998a): S86C.

    Google Scholar 

  • Lundstrom, K., A. Michel, H.D. Blasey, A.R. Bernard, R. Hovius, H. Vogel, and A. Surprenant. “Expression of ligand-gated ion channels with the Semhki Forest virus expression system”. J Receptor & Sign. Transd. Res. 17 (1997b): 115–128.

    Article  CAS  Google Scholar 

  • Lundstrom, K., A. Mills, G. Buell, E. Allet, N. Adami, and R Liljeström. “High-level expression of the human neurokinin-1 receptor in mammalian cell lines using the Semliki Forest virus expression system”. Eur J. Biochem. 224 (1994): 917–921.

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom, K., J.G. Richards, J.R. Pink, and F. Jenck. “Efficient in vivo expression of a reporter gene in rat brain after injection of recombinant replication-deficient Semliki Forest virus”. Gene Then Mol. Biol. 3 (1999a): 15–23.

    Google Scholar 

  • Lundstrom, K., D. Rotmann, D. Hermann, E.M. Schneider, and M.U. Ehrengruber. “Novel mutant Semliki Forest virus vectors: gene expression and locaUzation studies in neuronal cells”. Histochem. Cell Biol. 115 (2001): 83–91.

    PubMed  CAS  Google Scholar 

  • Lundstrom, K., C. Schweitzer, J.G. Richards, M.U. Ehrengruber, F. Jenck, and C. Miilhardt. “Semliki Forest virus vectors for in vitro and in vivo apphcations”. Gene Then Mol. Biol. 4 (1999b): 23–31.

    Google Scholar 

  • Lundstrom, K., and M.P. Turpin. “Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system”. Biochem. Biophys. Res. Comm. 225 (1996): 1068–1072.

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom, K., M.P. Turpin, C. Large, G. Robertson, P. Thomas, and X.Q. Lewell. “Mapping of the dopamine D3 receptor binding site by pharmacological characterizadon of mutants expressed in CHO cells with the Semliki Forest virus system”. J. Receptor & Sign. Transd. Res. 18 (1998b): 133–150.

    Article  CAS  Google Scholar 

  • Murphy, A.-M., M.M. Morris-Downes, B.J. Sheahan, and G.J. Atkins. “Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles”. Gene Then 7 (2000): 1477–1482.

    Article  CAS  Google Scholar 

  • Olkkonen, V.M., P. Liljeström, H. Garoff, K. Simons, and C. Dotti. “Expression of heterologous proteins in cultured rat hippocampal neurons using Semliki Forest virus vector”. J. Neurosci. Res. 35 (1993): 445–451.

    Article  PubMed  CAS  Google Scholar 

  • Perri, S., D.A. Driver, J.R Gardner, S. Sherrill, B.A. Belli, T.W. Dubensky Jr., and J.M. Polo. “Replicon vectors derived from Sindbis virus and Semliki Forest virus that estabhshed persistent replication in host cells”. J. Virol. 74 (2000): 9802–9807.

    Article  PubMed  CAS  Google Scholar 

  • Scheer, A., K. Björklöf, S. Cotecchia, and K. Lundstrom. “Expression of the αlB-adrenergic receptor and G protein subunits in mammalian cells using the Semliki Forest virus expression system”. J. Receptor & Sign. Transd. Res. 19 (1999): 369–378.

    Article  CAS  Google Scholar 

  • Schlaeger, E.-J., and K. Lundstrom. “Effect of temperatureon recombinant protein expression in Semliki Forest virus infected mammalian cell lines growing in serum-free suspension cultures”. Cytotechnology 28 (1998): 205–211.

    Article  PubMed  CAS  Google Scholar 

  • Smith, S.M., F. Maldarelli, and K.-T. Jeang. “Effiecient expression by an alphavirus replicon of a functional ribozyme targeted to human immunodeficiency virus type 1”. J. Virol. 71 (1997): 9713–9721.

    PubMed  CAS  Google Scholar 

  • Sjöberg, E.M., Suomalainen, M., and Garoff, H. “A significantly improved Semliki Forest virus expression system based on translation enhancer segments from the viral capsid gene”. Bio/Technology 12 (1994): 1127–1131.

    Article  PubMed  Google Scholar 

  • Xiong, C, R. Levis, P. Shen, S. Schlesinger, CM. Rice, and H.V Huang. “Sindbis virus: an efficient broad host range vector for gene expression in animal cells”. Science 243 (1989): 1188–1191.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Lundstrom, K. (2001). Application of Alphavirus Vectors in Drug Discovery. In: Lindner-Olsson, E., Chatzissavidou, N., Lüllau, E. (eds) Animal Cell Technology: From Target to Market. ESACT Proceedings, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0369-8_11

Download citation

  • DOI: https://doi.org/10.1007/978-94-010-0369-8_11

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-3897-3

  • Online ISBN: 978-94-010-0369-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics