Novel compound enables high-level adenovirus transduction in the absence of an adenovirus-specific receptor

FOULETIER-DILLING, C. M.; BOSCH, P.; DAVIS, A. R.; SHAFER, J. A.; STICE, S. L.; GUGALA, Z.; GANNON, F. H.; OLMEST-DAVIS, E. A.; (FOULETIER-DILLING, C. M. Y BOSCH, P. CONTRIBUYERON IGUALITARIAMENTE EN ESTE TRABAJO)

HUMAN GENE THERAPY

Mary Ann Liebert

Año: 2005 vol. 16 p. 1287 - 1297

1043-0342

Viral vectors are extensively used to deliver foreign DNA to cells for applications ranging from basic research to potential clinical therapies.  A limiting step in this process is virus uptake and internalization into the target cells which is mediated by membrane receptors.  Although it is possible to modify viral capsid proteins to target the viruses, such procedures are complex and often unsuccessful.  Here we present a rapid, inexpensive system for improving transduction of cells including those that lack receptors for adenovirus fiber proteins.  Addition of GeneJammer® during the adenovirus transduction led to both a significant increase in the total number of transduced cells as well as the level of transgene expression per cell.  Studies using cell lines deficient in adenovirus receptors demonstrated that addition of GeneJammer® provided a novel cellular-entry mechanism for the virus.  These findings were tested in a cell-based gene therapy system for the induction of bone, which is contingent on high level expression of the transgene.  Inclusion of GeneJammer® in either Ad5BMP2 or Ad5F35BMP2 transduction of a variety of cells including human peripheral blood, demonstrated a correlating increase in bone formation.  The results suggest a novel and versatile method for achieving high level transduction using adenovirus.