0000000000773380
AUTHOR
Joachim W. Engels
Chemical Synthesis of 2′-O-Alkylated siRNAs
Chemical synthesis has been a major endeavor to create active siRNAs. The downregulation of mRNA by 21-mer double-stranded siRNAs can be improved by using modified nucleotides, especially 2'-O-alkylated ones. Besides the commercially available 2 cent-O-methyl ribosides, 2'-alkyl groups bearing positive charges are especially promising candidates. We have shown that in a proper formulation they are superior to unmodified siRNAs. This may be due to enhanced stability and most probably to a better uptake into the cells.
Synergistic Anti-Human Immunodeficiency Viral (HIV-1) Effect of the Immunomodulator Ampligen (Mismatched Double-Stranded RNA) with Inhibitors of Reverse Transcriptase and HIV-1 Regulatory Proteins
The potent antiviral effect of double stranded RNA, such as the mismatched poly(l)·poly(C12U) [Ampligen], 2′,3′-dideoxy-3′-fluorothymidine (FddThd) and antisense oligodeoxynucleotides (ODN) has been established in in vitro systems using cells infected with the human immunodeficiency virus type 1 (HIV-1). We report here that the immunomodulator poly(l)·poly(C12U) interacts synergistically with (1) the reverse transcriptase inhibitor FddThd (FIC value: 0.43), (2) the modified (5′- and 3′-end capped thioates) antisense ODN-4 directed against the splice acceptor site of the HIV-1/ tat gene (FIC value: 0.66) and (3) also with pyronin Y, a compound which prevents binding of HIV-1 Rev protein to t…