Efficient expression by an alphavirus replicon of a functional ribozyme targeted to human immunodeficiency virus type 1.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Efficient expression by an alphavirus replicon of a functional ribozyme targeted to human immunodeficiency virus type 1.

J Virol. 1997 Dec;71(12):9713-21. Unique Identifier : AIDSLINE MED/98037688
Smith SM; Maldarelli F; Jeang KT; Laboratory of Molecular Microbiology, National Institute of Allergy; and Infectious Diseases, Bethesda, Maryland 20892-0460, USA.

Abstract: Intracellular applications of ribozymes have been limited partly by the availability of suitable high-expression systems. For RNA effectors, consideration of an RNA virus vector system for delivery and expression is reasonable. We show that alphavirus replicons can be highly efficient nonintegrating ribozyme-expressing vectors. Using a hammerhead ribozyme targeted to a highly conserved sequence in the U5 region of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat, we demonstrate that a full-length 8.3-kb Semliki Forest virus ribozyme (SFVRz) chimeric RNA maintains catalytic activity. SFVRz is packaged into viral particles, and these particles transduce mammalian cells efficiently. SFVRz-transduced BHK cells were found to produce large amounts of genomic and subgenomic forms of ribozyme-containing RNAs that are functional in cleaving a U5-tagged mRNA. The RNase protection assay shows that HIV-1 U5-chloramphenicol acetyltransferase mRNA expressed intracellularly from an RNA polymerase II promoter is quantitatively eliminated in SFVRz-transduced BHK cells.

Keywords: *HIV-1/METABOLISM *Replicon *RNA, Catalytic/BIOSYNTHESIS *Semliki Forest Virus/ENZYMOLOGY
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