Antisense Inhibition of Virus Infections

Kilkuskie, Robert E.; Field, Anjalie

doi:10.1016/s1054-3589(08)60147-7

Cited by 6 publications

(2 citation statements)

References 130 publications

(109 reference statements)

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“…Antisense nucleic acids offer hope as a source of new antiviral therapies: in vitro and in vivo experimental systems show that antisense nucleic acids can inhibit the replication of many viruses (Stein and Cheng, 1993; Kilkuskie, 1997; Wagner and Flanagan, 1997). But what of the long‐term prospects for this technology?…”

Section: Introductionmentioning

confidence: 99%

Viral escape from antisense RNA

Bull¹,

Jacobson²,

Badgett³

et al. 1998

Molecular Microbiology

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Section: Introductionmentioning

confidence: 99%

Viral escape from antisense RNA

Bull¹,

Jacobson²,

Badgett³

et al. 1998

Molecular Microbiology

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“…However, the rapid emergence of mutant viral strains resistant to these inhibitors continues to pose a constant threat to containing this disease. Another potentially important approach is the use of antisense nucleic acid complementary to the target sequence of HIV-1 genomic RNA to block both mRNA translation and viral replication (4). Although this approach is very promising, the uptake and the instability of the antisense oligonucleotides in the cells are problems yet to be overcome (5).…”

mentioning

confidence: 99%

Polyamide Nucleic Acid Targeted to the Primer Binding Site of the HIV-1 RNA Genome Blocks in Vitro HIV-1 Reverse Transcription

et al. 1998

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We report here that polyamide nucleic acid (PNA) as well as a polyamide nucleic acid-DNA chimera complementary to the primer binding site of the HIV-1 genome can completely block priming by tRNA3Lys and consequently the in vitro initiation of reverse transcription by HIV-1 RT. Conventional heating and cooling is not required for annealing PNA analogs to the complementary nucleotide sequence as effective blockage of reverse transcription results from their invasion in the duplex region of preprimed U5-PBS HIV-1 RNA template-primer and was seen even at ambient temperature. Further, the extension of the initiated nascent (-) strand DNA can also be blocked by inclusion of another PNA, targeted to upstream sequences in the U5 region of the viral RNA. Interestingly, a PNA chimera having only two DNA nucleotides annealed with the U5-PBS RNA is recognized as a bonafide primer by HIV-1 RT, as the 3'OH end of the chimeric molecule is extended by the enzyme in the presence of dNTPs. A significant observation was that RNA/PNA or RNA/(PNA-DNA) hybrids were entirely resistant to the RNase H activity of HIV-1 RT. Furthermore, PNA invasion into the RNA/DNA hybrid completely prevented the cleavage of the RNA strand, suggesting that the RNase H activity of HIV-1 RT which was required in reverse transcription may also be inhibited by the PNA oligomer. These observations suggest that oligomeric PNAs targeted to various critical regions of the viral genome are likely to have strong therapeutic potential for interrupting multiple steps involved in the replication of HIV-1 and warrant serious investigation especially in the area of an effective delivery system.

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Viral targets for antisense oligonucleotides: a mini review

Field

1998

Antiviral Research

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Antisense Inhibition of Virus Infections

Cited by 6 publications

References 130 publications

Viral escape from antisense RNA

Viral escape from antisense RNA

Polyamide Nucleic Acid Targeted to the Primer Binding Site of the HIV-1 RNA Genome Blocks in Vitro HIV-1 Reverse Transcription

Viral targets for antisense oligonucleotides: a mini review

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