Inhibition of HIV replication by immunoliposomal antisense oligonucleotide

Selvam, M P; Buck, Sheila M.; Blay, Roy A.; Mayner, Ronald E.; Mied, Paul; Epstein, Jay S.

doi:10.1016/s0166-3542(96)00993-x

Cited by 26 publications

(9 citation statements)

References 21 publications

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“…The use of antisense oligonucleotides has also emerged as a powerful new approach as antiviral agents (Selvam et al, 1996;Caselmann et al, 1997;Lima et al, 1997;Wagner and Flanagan, 1997;Veal et al, 1998). In fact, the initial therapeutic applications of ODN were supposed to be as an antiviral agent.…”

Section: Antisense Odn As Potential Drugs Inmentioning

confidence: 99%

Antisense oligonucleotides as therapeutic agents

1999

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Antisense oligonucleotides can block the expression of specific target genes involved in the development of human diseases. Therapeutic applications of antisense techniques are currently under investigation in many different fields. The use of antisense molecules to modify gene expression is variable in its efficacy and reliability, raising objections about their use as therapeutic agents. However, preliminary results of several clinical studies demonstrated the safety and to some extent the efficacy of antisense oligodeoxynucleotides (ODNs) in patients with malignant diseases. Clinical response was observed in some patients suffering from ovarian cancer who were treated with antisense targeted against the gene encoding for the protein kinase C-alpha. Some hematological diseases treated with antisense oligos targeted against the bcr/abl and the bcl2 mRNAs have shown promising clinical response. Antisense therapy has been useful in the treatment of cardiovascular disorders such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy. Antisense oligonucleotides also have shown promise as antiviral agents. Several investigators are performing trials with oligonucleotides targeted against the human immunodeficiency virus-1 (HIV-1) and hepatitis viruses. Phosphorothioate ODNs now have reached phase I and II in clinical trials for the treatment of cancer and viral infections, so far demonstrating an acceptable safety and pharmacokinetic profile for continuing their development. The new drug Vitravene, based on a phosphorothioate oligonucleotide designed to inhibit the human cytomegalovirus (CMV), promises that some substantial successes can be reached with the antisense technique.

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Section: Antisense Odn As Potential Drugs Inmentioning

confidence: 99%

Antisense oligonucleotides as therapeutic agents

1999

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“…A number of chemotherapeutic agents have been linked to proteins [11][12][13][14], monoclonal antibodies [15][16][17][18], polymers [19][20][21][22][23][24][25], particles or cationic lipids [26][27][28][29] and cyclodextrins [30].…”

Section: Introductionmentioning

confidence: 99%

2-Pyrrolinodoxorubicin and its peptide-vectorized form bypass multidrug resistance

Castex¹,

Mérida

Blanc

et al. 2004

Anti-Cancer Drugs

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A well-known mechanism leading to the emergence of multidrug-resistant tumor cells is the overexpression of P-glycoprotein, which is capable of lowering intracellular drug concentrations. In the present study, we tested the capability of 2-pyrrolinodoxorubicin (p-DOX), a highly potent derivative of DOX, to bypass multidrug resistance. The accumulation, intracellular distribution and cytotoxicity of p-DOX were tested in two cell lines (K562 and A2780) and their DOX-resistant counterparts (K562/ADR and A2780/ADR). Cellular accumulation and cytotoxicity were dramatically lowered for DOX in resistant cell lines, in comparison with non-resistant cells. In contrast, cellular accumulation, intracellular distribution and cytotoxicity of p-DOX were independent of the nature of the cell lines. The p-DOX showed potent dose-dependent inhibition of cell growth against resistant cells as compared with DOX. After treatment of resistant cells with verapamil, the intracellular levels of DOX were markedly increased and consequent cytotoxicity improved. In contrast, treatment of resistant cells with verapamil did not cause any further enhancement of cell uptake or an increase in the cytotoxic effect of the derivative p-DOX, indicating that the compound bypasses the P-glycoprotein. Finally, we show that vectorization of p-DOX by a peptide vector (SynB3) which has been shown to enhance the brain uptake of DOX and to decrease its heart accumulation does not affect this property. These results indicate that p-DOX and its vectorized form are potent and effective in overcoming multidrug resistance.

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“…Among these studies, target-specific inhibition of HIV-1 tat mRNA has been demonstrated targeting the splice site of tat intron I [23] and to some extent targeting p24 gag [25]. In contrast, targeting the region of translation initiation of HIV-1 rev (previously shown to be accessible to sequence-specific inhibition by fully modified ODNs [2,3,10,27,28]), neither sequence-dependent nor non-sequence-dependent inhibition of HIV-1 has been observed [21,22,24].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HIV-1 Replication by Chimeric Phosphorothioate Oligodeoxynucleotides Applied in Free Solution

Lund¹,

Hansen²

1998

Intervirology

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Oligodeoxynucleotides (ODNs) containing a variable number of 3′ and 5′ terminal phosphorothioate linkages were applied in free solution to cells infected by HIV-1. ODNs of 28 nt length were applied at up to 5 µM concentration. The ODNs were found to inhibit HIV-1 infection in a dose dependent manner, which correlated with the number of modified linkages (4, 8 and 12, respectively). A target sequence in the HIV-1 rev mRNA, previously reported as sensitive to antisense inhibition by full length phosphorothioate ODNs, only revealed non-sequence dependent inhibition of HIV-1, when tested by these modified chimers.

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Inhibition of HIV replication by immunoliposomal antisense oligonucleotide

Cited by 26 publications

References 21 publications

Antisense oligonucleotides as therapeutic agents

Antisense oligonucleotides as therapeutic agents

2-Pyrrolinodoxorubicin and its peptide-vectorized form bypass multidrug resistance

Inhibition of HIV-1 Replication by Chimeric Phosphorothioate Oligodeoxynucleotides Applied in Free Solution

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