Novel Tat-encoding bicistronic human immunodeficiency virus type 1-based gene transfer vectors for high-level transgene expression.
We describe bicistronic single-exon Tat (72-amino-acid Tat [Tat72])- and full-length Tat (Tat86)-encoding gene transfer vectors based on human immunodeficiency virus type 1 (HIV-1). We created versions of these vectors that were rendered Rev independent by using the constitutive transport element (CTE) from Mason-Pfizer monkey virus (MPMV). Tat72-encoding vectors performed better than Tat86-expressing vectors in gene transfer experiments. CTE-containing vectors, produced in a Rev-independent packaging system, had gene transfer efficiencies nearly equivalent to those produced using a combination RNA transport (CTE and Rev-Rev response element)-based packaging system. The Tat72-encoding vectors could be efficiently transduced into a variety of cell types, showed higher levels of transgene expression than vectors with the simian cytomegalovirus immediate-early or the simian virus 40 early promoter, and provide an alternative to HIV-1 vectors with internal promoters.
Srinivasakumar
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Division of Hematology-Oncology, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-6305, USA. narasimhachar.srinivasakumar@mcmail.vanderbilt.edu
Schuening
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D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D002460:Cell Line; D004285:Dogs; D005091:Exons; D015870:Gene Expression; D015696:Gene Products, tat / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D015215:Zidovudine / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D015215:Zidovudine