Herpes simplex virus type 1 thymidine kinase sequence fused to lacZ gene increases levels of -galactosidase activity per genome of high-capacity but not first generation adenoviral vectors in vitro and in vivo

PUNTEL; BARRET; MONDKAR; SAXENA; KROEGER; MUHAMMAD; LIU; BONDALE; SCIASCIA; XIONG; SHI; SALEM; ZADMER; HUYNH; PALMER; NG; CASTRO; LOWENSTEIN

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Año: 2009 p. 2004 - 2010

0022-538X

Increased transgene expression per vector genome is an important goal in theoptimization of viral vectors for gene therapy. Herein we demonstrate that herpes simplexvirus type 1 thymidine kinase (HSV1-TK) sequences (1131 bp) fused to the 3’ end oflacZ increases transgene expression from high capacity adenoviral vectors (HCAd), butnot from first generation (Ad) vectors. WPRE, in contrast, increased transgene expressionlevels from Ad, but not HCAd vectors. The differential activity of the HSV1-TK andWPRE sequences was detected both in vitro and in vivo, and suggests potential differentmechanisms of action, or the interaction of these elements with vector genomicsequences.