Visualizing a Correlation between siRNA Localization, Cellular Uptake, and RNAi in Living Cells

Chiu, Ya‐Lin; Ali, Akbar; Chu, Chin‐Chou; Cao, Hong; Rana, Tariq M.

doi:10.1016/j.chembiol.2004.06.006

Cited by 354 publications

(265 citation statements)

References 52 publications

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“…Tat, TP, and penetratin covalently linked to siRNA against luciferase, and GFP showed internalization and downregulation of gene expression (86,87). It has been further suggested that the cellular uptake of siRNA can be enhanced by noncovalent packaging with CPPs (88).…”

Section: Delivery Of Nucleic Acids By Cpp-mediated Cargo Deliverymentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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SummaryNovel classes and applications of cell-penetrating peptides (CPPs) are being constantly discovered since they were first identified 2 decades ago. These short cationic peptides (nanomolecules) either by covalent binding or by noncovalent binding can traverse cell membranes and deliver a variety of molecules that are unable to overcome the permeability barrier in their own capacity. The ability of the CPPs to deliver variety of macromolecules, such as oligonucleotides, therapeutic drugs, proteins, and medical imaging agents, by forming nanoparticulate carriers in a range of cells has led them to emerge as a potential tool for both macromolecule delivery application and to gain insight into the fundamentals of mechanism of cellular uptake across the plasma membrane. This review explores the recent advances, challenges, and future prospects in the field of CPP-mediated cargo delivery in mammalian and plant cells. Studies have been conducted into the peptide chemistry and stability of CPP-macromolecular complexes. Most of the CPPs have been shown to be nontoxic and do not interfere with the functionality of the macromolecules delivered across the cell membrane. The mechanism of uptake of CPP-cargo complexes and the uptake of CPPs alone across the plasma membrane remains unresolved. As the world of CPPs is rapidly advancing in both mammalian and plant system, there is a promising future for the various applications of transduction and transfection into intact cells.

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Section: Delivery Of Nucleic Acids By Cpp-mediated Cargo Deliverymentioning

confidence: 99%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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“…However, the combined challenges of intracellular delivery and unintended ''off-target'' effects remain formidable (4). The polyanionic nature and molecular size of siRNA are impediments to their entry into mammalian cells (5)(6)(7). In addition, siRNAs have both sequence-specific (8 -10) and sequence-independent (11-13) off-target effects, some of which are better understood than others.…”

mentioning

confidence: 99%

Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth

Cho

Albuquerque

Kleinman

et al. 2009

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

133

120

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Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.angiogenesis ͉ innate immunity ͉ lymphangiogenesis ͉ ischemia ͉ wound healing

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“…1, location of siRNA in perinuclear site showed that siRNA has entered the cells. Location in perinuclear site was correlated with the efficacy of RNAi [12].…”

Section: B Activation Of Crebmentioning

confidence: 99%

“…RNAi CREB is a process where intracellular pathway activation modulated by small-interfering RNA (siRNA) consisted of 21-23 nucleotides induces the degradation of specific mRNA target [12]. In Fig.…”

Section: B Activation Of Crebmentioning

confidence: 99%

The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

Triawanti¹,

Indra²,

Tjokroprawiro³

et al. 2014

IJCEA

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Abstract-One of the tissues taking the biggest part in the pathogenesis of obesity is adipose tissue mainly formed by white fat cells. Recently, the processes adipogenesis become a treatment target for obesity. One of the pathway that allegedly participated in the process of adipogenesis is activated via CREB. The upstream pathway is by means of protein of mammalian targets of rapamycin (mTOR). This study was aimed to determine the role of CREB in adipogenesis through the activation of p70S6K1 by mTORC1.This was an experimental study. Subjects were primary cultured preadipocytes taken from visceral fat of white rats (Rattus norvegicus). Cell cultures were classified into 4 groups: (K) Control of adipogenesis: without rapamycin and RNAi CREB, (A): was given rapamycin 10 nM, (B): was given RNAi CREB 100 nM, (C): was given rapamycin 10 nM and RNAi CREB 100 nM. p70S6K1, CREB activation, and expression of C/EBPδ measured on day 2, 4, and 6, and the morphology of adipocytes on day 6. Data were analyzed with Anova test, LSD test, and Pearson correlation test with 95% confidence level.The data showed that rapamycin activated p70S6K1 and caused lower CREB compared with control group during adipogenesis. These results indicated that adipogenesis was blocked, which resulted from the inhibition of p70S6K1 and CREB activation by rapamycin and RNAi CREB. The inhibition was stronger in rapamycin + RNAi CREB group. Statistically, there was significant correlation between p70S6K1 and CREB; and between CREB and C/EBPδ.It was concluded that the role of CREB in adipogenesis was mediated by the activation of p706K1 by mTORC1.Index Terms-Obesity, adipogenesis, mTORC1, p70S6K1, CREB, C/EBPδ.

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Visualizing a Correlation between siRNA Localization, Cellular Uptake, and RNAi in Living Cells

Cited by 354 publications

References 52 publications

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth

The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

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