Print Email Facebook Twitter Efficient targeting of adenoviral vectors to integrin positive vascular cells utilizing a CAR-cyclic RGD linker protein Title Efficient targeting of adenoviral vectors to integrin positive vascular cells utilizing a CAR-cyclic RGD linker protein Author Krom, Y.D. Gras, J.C.E. Frants, R.R. Havekes, L.M. van Berkel, T.J. Biessen, E.A.L. van Dijk, K.W. TNO Kwaliteit van Leven Publication year 2005 Abstract Vascular smooth muscle (VSMC) and endothelial cells (EC) are particularly resistant to infection by type 5 adenovirus (Ad) vectors. To overcome this limitation and target Ad vectors to ubiquitously expressed α Vβ3/5 integrins, we have generated a linker protein consisting of the extracellular domain of the coxsackie adenovirus receptor (CAR) connected via avidin to a biotinylated cyclic (c) RGD peptide. After optimization of CAR to cRGD and to Ad coupling, infection of mouse heart endothelial cells (H5V) could be augmented significantly, as demonstrated by 600-fold increased transgene expression levels. In EOMAs, a hemangioendothelioma-derived cell line, the fraction of infected cells was enhanced 4- to 6-fold. Furthermore, the fraction of infected primary mouse VSMC was increased from virtually 0% to 25%. Finally, in human umbilical vein endothelial cells, the number of GFP positive cells was enhanced from 2% to 75%. In conclusion, CAR-cRGD is a versatile and highly efficient construct to target Ad vectors to both transformed and primary VSMC and EC. © 2005 Elsevier Inc. All rights reserved. Chemicals / CAS: arginylglycylaspartic acid, 99896-85-2; arginyl-glycyl-aspartic acid, 99896-85-2; Integrin alphaVbeta3; integrin alphaVbeta5; Integrins; Oligopeptides; Receptors, Vitronectin; Recombinant Fusion Proteins Subject Biomedical ResearchAdenovirusCyclic RGD peptideEndothelial cellsTargetingVascular smooth muscle cellsadenovirus vectorarginylglycylaspartic acidavidincoxsackie virus and adenovirus receptorcyclopeptidegreen fluorescent proteinintegrinanimal cellanimal tissuebiotinylationcell fractionationcell lineendothelium cellgene expressiongene targetinghearthemangioendotheliomahuman cellinfectionmousenonhumanpriority journalprotein targetingtransgeneumbilical veinvascular smooth muscleAdenoviridaeAnimalsCHO CellsCricetinaeCricetulusGenetic VectorsHumansIntegrin alphaVbeta3IntegrinsMaleMiceMice, Inbred C57BLMuscle, Smooth, VascularMyocytes, Smooth MuscleOligopeptidesProtein EngineeringReceptors, VitronectinRecombinant Fusion ProteinsTransfectionAnimaliaCoxsackievirus To reference this document use: http://resolver.tudelft.nl/uuid:9a7f79b6-49b4-404e-bfc9-11a2ed873b17 DOI https://doi.org/10.1016/j.bbrc.2005.10.073 TNO identifier 239031 ISSN 0006-291X Source Biochemical and Biophysical Research Communications, 338 (2), 847-854 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.