Antisense inhibition of P-glycoprotein expression using peptide–oligonucleotide conjugates

Astriab-Fisher, Anna; Sergueev, Dimitri S.; Fisher, Michael H.; Shaw, Barbara Ramsay; Juliano, Rudolph L.

doi:10.1016/s0006-2952(00)00310-5

Cited by 163 publications

(95 citation statements)

References 29 publications

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“…On a molecular level, significant research has been devoted toward creating materials incorporating peptides and oligonucleotides because these types of chimeric structures have been shown to increase the knockdown of target proteins (34)(35)(36)(37)(38)(39)(40)(41)(42)(43). However, molecular methods of preparing these materials are relatively inefficient, limit sequence diversity because of incompatible chemistries, require orthogonal protecting groups on nucleosides and amino acids (44), and can generate undesired side products (45).…”

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confidence: 99%

“…GAPDH was used as the target because it is produced at high levels in most cell types and thus is representative of a general class of high-abundance proteins. The peptides used in this study were selected because of their demonstrated ability to increase cellular uptake and/or alter intracellular localization (34,35). In contrast to molecular materials, these conjugates can be purified and isolated simply by centrifugation and further allow the control of control oligonucleotide and peptide stoichiometries.…”

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confidence: 99%

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Peptide antisense nanoparticles

Patel

Giljohann

Seferos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

103

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We have designed a heterofunctionalized nanoparticle conjugate consisting of a 13-nm gold nanoparticle (Au NP) containing both antisense oligonucleotides and synthetic peptides. The synthesis of this conjugate is accomplished by mixing thiolated oligonucleotides and cysteine-terminated peptides with gold nanoparticles in the presence of salt, which screens interactions between biomolecules, yielding a densely functionalized nanomaterial. By controlling the stoichiometry of the components in solution, we can control the surface loading of each biomolecule. The conjugates are prepared easily and show perinuclear localization and an enhanced gene regulation activity when tested in a cellular model. This heterofunctionalized structure represents a new strategy for preparing nanomaterials with potential therapeutic applications.gene regulation ͉ gold nanoparticles ͉ heterofunctional

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confidence: 99%

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confidence: 99%

Peptide antisense nanoparticles

Patel

Giljohann

Seferos

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

103

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“…One striking feature of the peptide-ODN conjugates is that they inhibited P-glycoprotein expression more effectively in the presence of serum than in the absence of serum. Another study from the same group also showed the successful transportation of 2'-O-methyl PS-ODNs conjugated to TAT and Antp peptides to the cytoplasm as well as nucleus, leading to an increased pharmacological activity without compromising the specificity of antisense ODNs (531). In addition, a retro-inverso form of Ant was a peptidomimetic modification to confer more stability but still retain its activity and can rapidly be internalized and distribute throughout the cytoplasm and even the cell nucleus (532).…”

Section: Conjugation With Cell Penetrating Peptidesmentioning

confidence: 95%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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“…A short membrane active peptide, LK15 (KLLKLLLKLLLKLLK) was also conjugated onto tat 49-57 and used for plasmid transfection (Saleh et al, 2010). Antisense oligonucleotides were linked via disulfide bonds to cysteine-modified tat 49-60 and delivered into cells to inhibit the expression of P-glycoprotein, a transmembrane pump that is responsible for the multidrug resistance phenotype of tumor cells (Astriab-Fisher et al, 2000). siRNA has also been delivered by tat 47-57 and interestingly, photostimulation promoted the escape of tat complexes into the cytosol (Endoh et al, 2008).…”

Section: Tatmentioning

confidence: 99%