Peptide-Based Strategy for siRNA Delivery into Mammalian Cells

RNA Silencing ◽  
2005 ◽  
pp. 251-260 ◽  
Author(s):  
Federica Simeoni ◽  
May C. Morris ◽  
Frederic Heitz ◽  
Gilles Divita
Keyword(s):  
Mammalian Cells ◽  
Sirna Delivery

scholarly journals Pioneering siRNA-Mediated Protection of Mammalian Cells against Zika Virus (MR-766) Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 45
Author(s):  
Benedita K. L. Feron ◽  
Joachim J. Bugert ◽  
Simon C. W. Richardson
Keyword(s):  
Cell Viability ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Rna Binding ◽  
Sirna Delivery ◽  
Lethal Factor ◽  
Firefly Luciferase ◽  
Delivery Systems ◽  
Zikv Infection ◽  
Huh7 Cells

Here, we present empirical data documenting the siRNA-mediated protection of cells after Zika virus (ZIKV) infection. siRNAs were designed to target well-conserved sequences across the ZIKV genome. Several delivery technologies were utilized. After the electroporation of 100 nM siRNA into human hepatocyte-derived carcinoma (Huh7) cells, the Feron Zv-2 sequence (specific to the ZIKV NS3 gene) yielded a cell viability of 150.3% ± 7.4% (SEM: n = 4) (p = 0.0004) relative to the cells treated only with the virus (33.9% ± 12%, SEM: n = 4). Furthermore, 100 nM siRNA Feron Zv-4 (specific to ZIKV 3’UTR) resulted in 119.1% ± 11.2% cell viability (SEM: n = 4) relative to the control cells treated with ZIKV (p = 0.0021). The cells were electroporated with siRNA prior to ZIKV infection and viability was monitored four days after this. Additionally, two novel siRNA delivery systems were tested. The first utilized recombinant Bacillus anthracis PA83 (octomer-forming mutants), co-incubated with the N-terminal 255 amino acids of B. anthracis lethal factor (LFn) fused in-frame with the RNA binding domain for human protein kinase R (LFn-PKR) at a concentration of 50 µg/mL (each). Here, baby hamster kidney (BHK) cells, treated with 100 nM siRNA Feron Zv-1, yielded 79.0% ± 4.0% viability relative to the control (50.2% ± 1.7%, SEM: n = 3) three days after exposure to ZIKV (p = 0.0096). Finally, HeLa exosomes loaded with siRNA Feron-Zv2 were incubated with Huh7 cells prior to ZIKV infection. For the siRNA-exosome treated cells, a viability of 123% ± 46% (SEM: n = 18), relative to 8% ± 16% (SEM: n = 18) for the same concentration of control HeLa exosomes, was recorded (p = 0.0416). In each instance, 0.3 moI was used and cell viability monitored using the PierceTM Firefly Luciferase Glow Assay Kit by Thermo ScientificTM. Here, we show for the first time that siRNA can significantly reduce ZIKV-induced cell killing. Future work will require quantitating ZIKV mRNA in relation to siRNA treatment, as well as testing the siRNAs and delivery systems within more complex models.

Recent advances in siRNA delivery

2015 ◽  
Vol 6 (5-6) ◽  
pp. 321-341 ◽  
Author(s):  
Can Sarisozen ◽  
Giuseppina Salzano ◽  
Vladimir P. Torchilin
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Sirna Delivery ◽  
Potential Treatment ◽  
Small Interfering Rnas ◽  
Altered Gene Expression ◽  
The Past ◽  
Clinical Reality ◽  
Recent Advances ◽  
Altered Gene

AbstractIn the 1990s an unexpected gene-silencing phenomena in plants, the later called RNA interference (RNAi), perplexed scientists. Following the proof of activity in mammalian cells, small interfering RNAs (siRNAs) have quickly crept into biomedical research as a new powerful tool for the potential treatment of different human diseases based on altered gene expression. In the past decades, several promising data from ongoing clinical trials have been reported. However, despite surprising successes in many pre-clinical studies, concrete obstacles still need to be overcome to translate therapeutic siRNAs into clinical reality. Here, we provide an update on the recent advances of RNAi-based therapeutics and highlight novel synthetic platforms for the intracellular delivery of siRNAs.

scholarly journals A Cell-penetrating Helical Polymer For siRNA Delivery to Mammalian Cells

2012 ◽  
Vol 20 (8) ◽  
pp. 1599-1609 ◽  
Author(s):  
Nathan P Gabrielson ◽  
Hua Lu ◽  
Lichen Yin ◽  
Kyung Hoon Kim ◽  
Jianjun Cheng
Keyword(s):  
Mammalian Cells ◽  
Sirna Delivery ◽  
Helical Polymer ◽  
Cell Penetrating ◽  
A Cell

Making drugs safer: improving drug delivery and reducing the side effect of drugs on the human biochemical system

2016 ◽  
Vol 5 (2) ◽  
Author(s):  
Arome Odiba ◽  
Chimere Ukegbu ◽  
Oluchukwu Anunobi ◽  
Ike Chukwunonyelum ◽  
Juliet Esemonu
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Mammalian Cells ◽  
Near Infrared ◽  
Polymeric Micelles ◽  
Phenylboronic Acid ◽  
Sirna Delivery ◽  
Matrix Metalloproteinase 2 ◽  
Transepithelial Transport ◽  
Unintended Effects

AbstractRestrategizing becomes inevitable when in trying to proffer solution to a problem, damage in a different form is done. The unintended effects of drugs (side effects) could be leaving behind more damage than the therapeutic effect they are required to provide. This has led to the withdrawal of a number of drugs. However, there are still a number of options to explore in delivery, especially in the application of nanomedicine. Such advances in nanomedicine employ the use of phenylboronic acid-installed polymeric micelles, matrix metalloproteinase 2-sensitive poly(ethylene glycol)-drug conjugate, multifunctional DNA nanoflowers, single vehicular delivery of small interfering RNA (siRNA), nanoparticle-mediated codelivery of siRNA and prodrug, lipopeptide nanoparticles for siRNA delivery, ferrous iron-dependent drug delivery, polyprodrug amphiphiles, transepithelial transport of Fc-targeted nanoparticles, mutant KRAS target, monovalent molecular shuttle, near-infrared-actuated devices, transferrin receptor trafficking, remote loading of preencapsulated drugs, ATP-mediated liposomal drug delivery, nanoparticle-based combination chemotherapy delivery system, nucleic acid nanoparticle conjugates, ultrasound-triggered disruption of cross-linked hydrogels, refilling drug delivery depots through the blood, siRNA payloads to target KRAS-mutant cancer, delivery of antibody mimics into mammalian cells, biologically “smart” hydrogel, combination of liposomes containing bio-enhancers, and tetraether lipids. Minimized side effects, increased bioavailability, and reduced dosage are possible benefits of improved drug targeting.

Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles

Biomaterials ◽  
2010 ◽  
Vol 31 (7) ◽  
pp. 1821-1829 ◽  
Author(s):  
Katharina Ladewig ◽  
Marcus Niebert ◽  
Zhi P. Xu ◽  
Peter P. Gray ◽  
Gao Q.M. Lu
Keyword(s):  
Layered Double Hydroxide ◽  
Mammalian Cells ◽  
Sirna Delivery ◽  
Double Hydroxide ◽  
Layered Double Hydroxide Nanoparticles

scholarly journals Fabrication and intracellular delivery of siRNA/carbonate apatite nano-composites for effective knockdown of cyclin B1 gene

2011 ◽  
Vol 1 (1) ◽  
pp. 8 ◽  
Author(s):  
Anthony Stanislaus ◽  
Sharif Hossain ◽  
Ming Jang Chua ◽  
Anil Philip Kunnath ◽  
Quek Chia Wen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mammalian Cells ◽  
Sirna Delivery ◽  
Intracellular Delivery ◽  
Cyclin B1 ◽  
Transcriptional Level ◽  
Carbonate Apatite ◽  
Dependent Manner ◽  
B1 Gene ◽  
Cervical Cancer Cells

<p>Gene therapy through intracellular delivery of a functional gene or a gene-silencing element is a promising approach to properly treat critical human diseases like cancer. The ability of synthetically designed small interfering RNA (siRNA) to effectively silence genes<em> </em>at post-transcriptional level has made them attractive options in targeted therapeutics. However, naked siRNA being unable to passively diffuse through cellular membranes, poses difficulty in fully exploiting the potential of the technology. pH-sensitive carbonate apatite has been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and effective cellular endocytosis. Moreover, internalized siRNA has been found to escape from the endosomes in a time-dependent manner and effectively silenced reporter gene expression. Knockdown of cyclin B1 gene with only 10 nM of siRNA delivered by carbonate apatite has resulted in significant death of cervical cancer cells. Moreover, delivery of siRNA against cyclin B1 gene has led to the sensitization of the cancer cells to both cisplatin and doxorubicin at a particulat drug concentration. Thus, the new method of siRNA delivery is highly promising for pre-clinical and clinical cancer therapy using siRNA therapeutics.</p>

scholarly journals A New Potent Secondary Amphipathic Cell–penetrating Peptide for siRNA Delivery Into Mammalian Cells

2009 ◽  
Vol 17 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Laurence Crombez ◽  
Gudrun Aldrian-Herrada ◽  
Karidia Konate ◽  
Quan N Nguyen ◽  
Gary K McMaster ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Sirna Delivery ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating
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