254 Nucleic Acids Research, 2007, Vol. 35, No. 1 RNAi to achieve a signiﬁcant barrier to HIV-1 replication (39–42). While the U1 snRNA based strategy would affect the nuclear metabolism of the viral RNA, RNAi could be used to reduce the concentration of the same RNA in the cytoplasm, the location of the RISC complex. Future work will focus on expanding the number of U1 snRNA variants with anti-HIV-1 activity and exploration of the durability of the response to multiple viral strains and detection of resistant HIV-1 variants following serial passages of virus on cells expressing these constructs. The demonstrated efﬁcacy of this approach for HIV-1 suggests it may prove of equal value in the suppression of replication of other viruses which display a similar reliance on the host cell polyadenylation machinery for replication. ACKNOWLEDGEMENTS K.A. was supported by a scholarship from CIHR while A.C. is an OHTN scientist. Research was supported by a grant from OHTN. 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