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Nanotherapeutics Using an HIV-1 Poly A and Transactivator of the HIV-1 LTR-(TAR-) Specific siRNA.

Mahajan SD, Aalinkeel R, Reynolds JL, Nair B, Sykes DE, Law WC, Ding H, Bergey EJ, Prasad PN, Schwartz SA - Patholog Res Int (2011)

Bottom Line: We used a well-validated siRNA (si510) which targets the poly A/TAR (transactivator of the HIV-1 LTR) site and suppresses viral replication.Our results suggest that the QR-si510 HIV-1 siRNA nanoplex is not only effective in delivering siRNA, but also in suppressing HIV-1 viral replication for a longer time period.HIV-1 nanotherapeutics can thus enhance systemic bioavailability and offer multifunctionality.

View Article: PubMed Central - PubMed

Affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University at Buffalo, The State University of New York, 640 Ellicott Street, Room 444 Innovation Center, Buffalo, NY 14203, USA.

ABSTRACT
HIV-1 replication can be efficiently inhibited by intracellular expression of an siRNA targeting the viral RNA. We used a well-validated siRNA (si510) which targets the poly A/TAR (transactivator of the HIV-1 LTR) site and suppresses viral replication. Nanotechnology holds much potential for impact in the field of HIV-1 therapeutics, and nanoparticles such as quantum rods (QRs) can be easily functionalized to incorporate siRNA forming stable nanoplexes that can be used for gene silencing. We evaluated the efficacy of the QR-si510 HIV-1 siRNA nanoplex in suppressing viral replication in the HIV-1-infected monocytic cell line THP-1 by measuring p24 antigen levels and gene expression levels of HIV-1 LTR. Our results suggest that the QR-si510 HIV-1 siRNA nanoplex is not only effective in delivering siRNA, but also in suppressing HIV-1 viral replication for a longer time period. HIV-1 nanotherapeutics can thus enhance systemic bioavailability and offer multifunctionality.

No MeSH data available.


Related in: MedlinePlus

QR-si510 siRNA nanoplex characterization: Representative figures of (a) Transmission electron microscope image of nanoplexes showing that the average diameter of the nanoplex is ~15–20 nm (bar scale = 50 nm). No aggregation was observed after nanoplex formation. (b) Absorption (red line) and Emission spectra (green line) of QR-si510 siRNA nanoplexes.
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fig1: QR-si510 siRNA nanoplex characterization: Representative figures of (a) Transmission electron microscope image of nanoplexes showing that the average diameter of the nanoplex is ~15–20 nm (bar scale = 50 nm). No aggregation was observed after nanoplex formation. (b) Absorption (red line) and Emission spectra (green line) of QR-si510 siRNA nanoplexes.

Mentions: The physical properties of the nanoparticle formulations are usually established using the following techniques: (a) dynamic light scattering to estimate the hydrodynamic diameter and surface charge of the aqueous dispersed nanoparticles, (b) transmission electron microscopy (TEM) to determine particle size and size distribution, and (c) evaluation of the spectral properties of the fluorescent nanomaterials using simple spectrophotometry and spectrofluorimetry. Figure 1 shows the size-distribution of the QR-siRNA nanoplex via TEM and DLS measurements. TEM image (Figure 1(a)) shows the rods with average length and diameter of 15 nm. Figure 1(b) shows the absorption and emission spectra of the free siRNA and the siRNA bound to the QR with the QR emission wavelength around ~620 nm. Transmission electron microscopy (TEM) images of nanoplexes show that they remain as individual particles with a diameter of ~15–20 nm (Figure 1(a)). It can be visualized from the TEM that siRNA complexation did not cause any aggregation of the QRs. The concentration of these positively charged QRs was approximately 0.1 mg/mL and the optimal concentration of QR that was used to conjugate with the si510 HIV-1 siRNA to form a nanoplex was 200 pg.


Nanotherapeutics Using an HIV-1 Poly A and Transactivator of the HIV-1 LTR-(TAR-) Specific siRNA.

Mahajan SD, Aalinkeel R, Reynolds JL, Nair B, Sykes DE, Law WC, Ding H, Bergey EJ, Prasad PN, Schwartz SA - Patholog Res Int (2011)

QR-si510 siRNA nanoplex characterization: Representative figures of (a) Transmission electron microscope image of nanoplexes showing that the average diameter of the nanoplex is ~15–20 nm (bar scale = 50 nm). No aggregation was observed after nanoplex formation. (b) Absorption (red line) and Emission spectra (green line) of QR-si510 siRNA nanoplexes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108557&req=5

fig1: QR-si510 siRNA nanoplex characterization: Representative figures of (a) Transmission electron microscope image of nanoplexes showing that the average diameter of the nanoplex is ~15–20 nm (bar scale = 50 nm). No aggregation was observed after nanoplex formation. (b) Absorption (red line) and Emission spectra (green line) of QR-si510 siRNA nanoplexes.
Mentions: The physical properties of the nanoparticle formulations are usually established using the following techniques: (a) dynamic light scattering to estimate the hydrodynamic diameter and surface charge of the aqueous dispersed nanoparticles, (b) transmission electron microscopy (TEM) to determine particle size and size distribution, and (c) evaluation of the spectral properties of the fluorescent nanomaterials using simple spectrophotometry and spectrofluorimetry. Figure 1 shows the size-distribution of the QR-siRNA nanoplex via TEM and DLS measurements. TEM image (Figure 1(a)) shows the rods with average length and diameter of 15 nm. Figure 1(b) shows the absorption and emission spectra of the free siRNA and the siRNA bound to the QR with the QR emission wavelength around ~620 nm. Transmission electron microscopy (TEM) images of nanoplexes show that they remain as individual particles with a diameter of ~15–20 nm (Figure 1(a)). It can be visualized from the TEM that siRNA complexation did not cause any aggregation of the QRs. The concentration of these positively charged QRs was approximately 0.1 mg/mL and the optimal concentration of QR that was used to conjugate with the si510 HIV-1 siRNA to form a nanoplex was 200 pg.

Bottom Line: We used a well-validated siRNA (si510) which targets the poly A/TAR (transactivator of the HIV-1 LTR) site and suppresses viral replication.Our results suggest that the QR-si510 HIV-1 siRNA nanoplex is not only effective in delivering siRNA, but also in suppressing HIV-1 viral replication for a longer time period.HIV-1 nanotherapeutics can thus enhance systemic bioavailability and offer multifunctionality.

View Article: PubMed Central - PubMed

Affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Medicine, University at Buffalo, The State University of New York, 640 Ellicott Street, Room 444 Innovation Center, Buffalo, NY 14203, USA.

ABSTRACT
HIV-1 replication can be efficiently inhibited by intracellular expression of an siRNA targeting the viral RNA. We used a well-validated siRNA (si510) which targets the poly A/TAR (transactivator of the HIV-1 LTR) site and suppresses viral replication. Nanotechnology holds much potential for impact in the field of HIV-1 therapeutics, and nanoparticles such as quantum rods (QRs) can be easily functionalized to incorporate siRNA forming stable nanoplexes that can be used for gene silencing. We evaluated the efficacy of the QR-si510 HIV-1 siRNA nanoplex in suppressing viral replication in the HIV-1-infected monocytic cell line THP-1 by measuring p24 antigen levels and gene expression levels of HIV-1 LTR. Our results suggest that the QR-si510 HIV-1 siRNA nanoplex is not only effective in delivering siRNA, but also in suppressing HIV-1 viral replication for a longer time period. HIV-1 nanotherapeutics can thus enhance systemic bioavailability and offer multifunctionality.

No MeSH data available.


Related in: MedlinePlus