ABSTRACT Previously, we demonstrated that recombinant Semliki Forest virus (SFV) vector rapidly and selectively transfers genes into cultured vascular smooth muscle cells (VSMC), leaving

endothelial cells (EC) unaffected. From this, we hypothesized that recombinant SFV _in vivo_ only transfers genes into the media of balloon-injured but not intact vessel, that gene

expression in VSMC is fast, and that the specificity of SFV for VSMC is caused by specific binding sites. To address these hypotheses, we studied the time course of _in vivo_ SFV-LacZ and

Ad-LacZ expression in balloon-injured rat aorta. In addition, the fusion characteristics of fluorescent pyrene-labeled SFV were explored in cultured VSMC and EC. In intact aorta, no LacZ

SFV showed that fusion was higher and, moreover, saturable in VSMC as compared with EC, indicating the presence of specific SFV binding sites on VSMC, but not EC. From this we conclude that

_in vivo_ selectivity of SFV in balloon-injured vessels is based on the removal of the endothelium, which results in accessibility of VSMC in the media that carry specific binding sites for

the SFV vector. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

Subscribe to this journal Receive 6 print issues and online access $259.00 per year only $43.17 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full

article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs *

Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NOVEL EXPRESSION CASSETTES FOR INCREASING APOLIPOPROTEIN AI TRANSGENE EXPRESSION IN VASCULAR ENDOTHELIAL CELLS Article Open

access 06 December 2022 AAV LIBRARY SCREENING IDENTIFIES NOVEL VECTOR FOR EFFICIENT TRANSDUCTION OF HUMAN AORTA Article Open access 18 December 2024 AAV DELIVERY STRATEGY WITH MECHANICAL

SUPPORT FOR SAFE AND EFFICACIOUS CARDIAC GENE TRANSFER IN SWINE Article Open access 01 December 2024 REFERENCES * Feldman L.J., Tahlil O., Steg G. . Perspectives of arterial gene therapy for

the prevention of restenosis _Cardiovasc Res_ 1996 32: 194 194 Article  CAS  PubMed  Google Scholar  * Feldman L.J., Steg G. . Optimal techniques for arterial gene transfer _Cardiovasc Res_

1997 35: 391 391 Article  CAS  PubMed  Google Scholar  * Roks A.J.M. _et al_. Vectors based on Semliki Forest virus for rapid and efficient gene transfer into non-endothelial cardiovascular

cells: comparison to adenovirus _Cardiovasc Res_ 1997 35: 498 498 Article  CAS  PubMed  Google Scholar  * Sjöberg E.M., Suomalainen M., Garoff H. . A significantly improved Semliki Forest

virus expression system based on translation enhancer segments from the viral capsid gene _Bio/technol_ 1994 12: 1127 1127 Article  Google Scholar  * Liljeström P., Garoff H. . A new

generation of animal cell expression vectors based on the Semliki Forest virus replicon _Bio/technol_ 1991 9: 1356 1356 Article  Google Scholar  * Berglund P. _et al_. Semliki Forest virus

expression system: production of conditionally infectious recombinant particles _Bio/technol_ 1993 11: 916 916 CAS  Google Scholar  * Smerdou C., Liljeström P. . Two-helper RNA system for

production of recombinant Semliki Forest virus particles _J Virol_ 1993 73: 1535 1535 Google Scholar  * Schulick A.H. _et al_. Endothelium-specific in vivo gene transfer _Circ Res_ 1995 77:

475 475 Article  CAS  PubMed  Google Scholar  * Kim S. _et al_. Transcriptional targeting of replication-defective adenovirus transgene expression to smooth muscle cells _in vivo_ _J Clin

Invest_ 1997 100: 1006 1006 Article  CAS  PubMed  PubMed Central  Google Scholar  * Soiluhänninen M. _et al_. Semliki forest virus infects mouse brain endothelial cells and causes

blood–brain barrier damage _J Virol_ 1994 68: 6291 6291 Google Scholar  * Atkins G.J., Sheahan B.J., Liljeström P. . The molecular pathogenesis of Semliki Forest virus: a model virus made

useful? _J Gen Virol_ 1999 80: 2287 2287 Article  CAS  PubMed  Google Scholar  * Varenne O. _et al_. Percutaneous adenoviral gene transfer into porcine coronary arteries: is catheter-based

gene delivery adapted to coronary circulation? _Hum Gene Ther_ 1999 10: 1105 1105 Article  CAS  PubMed  Google Scholar  * Bult H. . Restenosis: a challenge for pharmacology _Trends Pharmacol

Sci_ 2000 21: 274 274 Article  CAS  PubMed  Google Scholar  * Lee S.W. _et al_. _In vivo_ adenoviral vector-mediated gene transfer into balloon-injured rat carotid arteries _Circ Res_ 1993

73: 797 797 Article  CAS  PubMed  Google Scholar  * Kafri T. _et al_. Cellular immune response to adenoviral vector infected cells does not require _de novo_ viral gene expression:

implications for gene therapy _Proc Natl Acad Sci USA_ 1998 95: 11377 11377 Article  CAS  PubMed  PubMed Central  Google Scholar  * Dryga S.A., Dryga O.A., Schlesinger S. . Identification of

mutations in a Sindbis virus variant able to establish persistant infection in BHK cells: the importance of a mutation in the nsP2 gene _Virology_ 1997 228: 74 74 Article  CAS  PubMed 

Google Scholar  * Scallan M.F., Allsopp T.E., Fazakerley J.K. . Bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death _J Virol_ 1997

71: 1583 1583 CAS  PubMed  PubMed Central  Google Scholar  * Haisma H.J. _et al_. Targeting of adenoviral vectors through a bispecific single-chain antibody _Cancer Gene Ther_ 2000 7: 901

901 Article  CAS  PubMed  Google Scholar  * Stegmann T. _et al_. Evaluation of viral membrane fusion assays. Comparison of the octadecylrhodamine dequenching assay with the pyrene excimer

assay _Biochemistry_ 1993 32: 11130 11130 Article  Google Scholar  * Filipeanu C.M., Henning R.H., de Zeeuw D., Nelemans A. . Intracellular angiotensin II and cell growth of vascular smooth

muscle cells _Br J Pharmacol_ 2001 132: 1590 1590 Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We are very grateful to Hans Bartels, Alexandra

Beuving, Martin Houwertjes, Gera Kamps, Bianca Meijeringh, Egbert Scholtens, Lucia van der Veen, and Jetti van Wijk, for their technical support. We thank Dr A Suurmeijer of the Department

of Pathology, University Hospital Groningen for his useful suggestions. Further, we thank Medtronic-Bakken Research Maastricht, Inex Pharmaceuticals (grant to J Wilschut), and the

Netherlands Heart Foundation (ICIN grant No. 295-0019 to Dr RA Tio) for their financial support. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Clinical Pharmacology, Groningen

University Institute for Drug Exploration (GUIDE), University of Groningen, The Netherlands A J M Roks, R H Henning, H Buikema, D de Zeeuw & W H van Gilst * Department of Cardiology,

University of Groningen, The Netherlands Y M Pinto & R A Tio * Department of Medical Microbiology, Molecular Virology Section, University of Groningen, The Netherlands M J J Kraak & 

J Wilschut * Department of Therapeutic Gene Modulation, University of Groningen, The Netherlands H J Haisma Authors * A J M Roks View author publications You can also search for this author

inPubMed Google Scholar * R H Henning View author publications You can also search for this author inPubMed Google Scholar * H Buikema View author publications You can also search for this

author inPubMed Google Scholar * Y M Pinto View author publications You can also search for this author inPubMed Google Scholar * M J J Kraak View author publications You can also search for

this author inPubMed Google Scholar * R A Tio View author publications You can also search for this author inPubMed Google Scholar * D de Zeeuw View author publications You can also search

for this author inPubMed Google Scholar * H J Haisma View author publications You can also search for this author inPubMed Google Scholar * J Wilschut View author publications You can also

search for this author inPubMed Google Scholar * W H van Gilst View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Roks, A., Henning, R., Buikema, H. _et al._ Recombinant Semliki Forest virus as a vector system for fast and selective _in vivo_ gene

delivery into balloon-injured rat aorta. _Gene Ther_ 9, 95–101 (2002). https://doi.org/10.1038/sj.gt.3301632 Download citation * Received: 15 November 2001 * Accepted: 16 November 2001 *

Published: 22 February 2002 * Issue Date: 01 January 2002 * DOI: https://doi.org/10.1038/sj.gt.3301632 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

KEYWORDS * Semliki Forest virus * adenovirus * vascular smooth muscle cells * endothelial cells * rat aorta * balloon injury * gene therapy