A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1

Kinchington, D.; Galpin, S.; Jaroszewski, Jerzy W.; Ghosh, Krishna; Subasinghe, C.; Cohen, Jack S.

doi:10.1016/0166-3542(92)90090-r

Cited by 49 publications

(26 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mechanism is conventionally termed in the literature and in this report as "antisense." It is well established that [26][27][28][29][30][31][32] antisense ODNs might have, in addition, activity that is related to a "non-antisense" effect (ie, not related to an antisense effect) as we have referred to it here. This non-antisense effect can be due to multiple mechanisms comprising those originating from the activity of a specific ODN sequence (termed here as a "sequence-specific" effect) and those originating from the activity of an ODN that is not specific to a particular sequence (termed here as a "non-sequence-specific" effect).…”

Section: Experimental Protocol Designmentioning

confidence: 99%

“…It is possible that release of ILs, such as INF-gamma, tumor necrosis factor , or IL-12, may be involved in anti-HIV activity in the assays used in this study, thus contributing to the random ODNs' high activity. PS-ODNs have been shown to inhibit the replication of HIV-1 in vitro by both sequencespecific 19,29,37,38 and non-sequence-specific [29][30][31][32] processes depending on the cell culture model employed. In acute-infection models, non-antisense inhibition of PS-ODNs has been well documented 1 and might occur, because of interference with virus adsorption, by binding to the CD4 receptor or the V3 loop of viral gp120, [39][40][41] or with reverse transcription.…”

Section: Previously Described Non-specific Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

et al. 2002

View full text Add to dashboard Cite

Section: Experimental Protocol Designmentioning

confidence: 99%

Section: Previously Described Non-specific Effectsmentioning

confidence: 99%

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

et al. 2002

View full text Add to dashboard Cite

“…1). Native (phosphodiester) antisense oligonucleotides have generally been reported to have little (2) or no inhibitory effect against HIV-1 in culture (3)(4)(5) because they are rapidly degraded in culture medium (6)(7)(8). Two approaches exist to circumvent this degradation.…”

Section: Introductionmentioning

confidence: 99%

“…These include phosphorothioate oligonucleotides and oligonucleotides with the sugar moiety oriented in the at configuration. Phosphorothioate oligonucleotides have been shown to inhibit the replication of HIV-1 in vitro by both sequence-non-specific (3,5,10,11) and specific processes (12)(13)(14)(15)(16), depending on the type of infection. In acutely infected cells, phosphorothioate oligonucleotides acted in a sequence-non-specific fashion probably by inhibition of viral binding and fusion (17,18) and/or viral reverse transcriptase (RT) (19,20).…”

Section: Introductionmentioning

confidence: 99%

Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms

Zelphati¹,

Imbach²,

Signoret³

et al. 1994

Nucl Acids Res

View full text Add to dashboard Cite

Phosphodiester and phosphorothioate oligonucleotides in a and , configurations directed against the initiation codon region of the HIV-1 rev gene were evaluated for their ability to inhibit HIV-1 replication in acutely and chronically infected human CEM cells. Encapsulation in antibody-targeted liposomes (immunoliposomes) permitted intracellular delivery and distinction between oligonucleotide-mediated inhibition of viral entry and intracellular effects on viral RNA. Our results are consistent with four mechanisms of antiviral activity for these antisense oligonucleotides: (i) interference with virus-mediated cell fusion by free but not liposome-encapsulated phosphorothioate oligonucleotides of any sequence; (ii) interference with reverse transcription in a sequence non-specific manner by phosphorothioate oligonucleotides in a and a configurations; (iii) interference with viral reverse transcription in a sequence-specific and RNase-H-independent manner by a and (3 phosphodiester oligonucleotides; (iv) interference with viral mRNA in a sequence-specific and RNase-H-dependent manner by 0-phosphorothioate oligonucleotides.

show abstract

“…In previous studies, we and others have shown that phosphodiester oligonucleotides free in solution were unable to inhibit HIV replication (up to a concentration of 50 /zM) because their degradation by extracellular nucleases is rapid and their uptake relatively poor (Matsukura et al, 1987;Kim et al, 1991;Kinchington et al, 1992;Zelphati et al, 1993). To protect oligonucleotides from nuclease action and to concentrate them at the cell surface we encapsulated oligonucleotides or incorporated oligonucleotides coupled to cholesterol in liposomes and evaluated their antiviral activity.…”

Section: Antiviral Effects Of Oligonucleotides Encapsulated or Incorpmentioning

confidence: 99%

Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes

1994

View full text Add to dashboard Cite

Encapsulation of oligonucleotides in antibody-targeted liposomes (immunoliposomes) which bind to target cells permits intracellular delivery of the oligonucleotides. This approach circumvents problems of extracellular degradation by nucleases and poor membrane permeability which free phosphodiester oligonucleotides are subject to, but leaves unresolved the inefficiency of encapsulation of oligonucleotides in liposomes. We have coupled oligonucleotides to cholesterol via a reversible disulfide bond. This modification of oligonucleotides improved their association with immunoliposomes by a factor of about 10 in comparison to unmodified oligonucleotides. The presence of cholesteryl-modified oligonucleotides incorporated in the bilayer of liposomes did not interfere with the coupling of the targeting protein to the liposome surface. Free or cholesterol coupled oligonucleotides associated with liposomes and directed against the tat gene of HIV-1 were tested for inhibition of HIV-1 proliferation in acutely infected cells. We demonstrate that the cholesteryl-modified as well as unmodified oligonucleotides acquire the target specificity of the antibody on the liposome. Their antiviral activity when delivered into cells is sequence-specific. The activity of these modified or unmodified oligonucleotides to inhibit the replication of HIV was the same on an equimolar basis (ECs0 around 0.1 /~M). Cholesterol coupled oligonucleotides thus offer increased liposome association without loss of antiviral activity.

show abstract

A comparison of gag, pol and rev antisense oligodeoxynucleotides as inhibitors of HIV-1

Cited by 49 publications

References 18 publications

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

Is antisense an appropriate nomenclature or design for oligodeoxynucleotides aimed at the inhibition of HIV-1 replication?

Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms

Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes

Contact Info

Product

Resources

About