Versatility of cell-penetrating peptides for intracellular delivery of siRNA

Singh, T. P.; Murthy, Akula S. N.; Yang, Hyejin; Im, Jungkyun

doi:10.1080/10717544.2018.1543366

Cited by 55 publications

(37 citation statements)

References 110 publications

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“…Cell-penetrating peptides (CPPs) have attracted increasing attention for RNA delivery due to their versatility and cell entry ability [ 54 ]. The design of peptide sequence can be inspired by natural peptides, proteins with known functions, or by computational simulation [ 55 , 56 ].…”

Section: Rna Delivery Vectors For Pulmonary Deliverymentioning

confidence: 99%

Inhaled RNA Therapy: From Promise to Reality

Chow

Qiu

Lam

2020

Trends in Pharmacological Sciences

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RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains identifying a safe and effective delivery system. Studies investigating RNA therapeutics in pulmonary diseases have rapidly expanded and drug administration by inhalation allows the direct delivery of RNA therapeutics to the target site of action while minimizing systemic exposure. In this review, we highlight recent developments in pulmonary RNA delivery systems with the use of nonviral vectors. We also discuss the major knowledge gaps that require thorough investigation and provide insights that will help advance this exciting field towards the bedside.

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Section: Rna Delivery Vectors For Pulmonary Deliverymentioning

confidence: 99%

Inhaled RNA Therapy: From Promise to Reality

Chow

Qiu

Lam

2020

Trends in Pharmacological Sciences

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“…The latter approach has been successfully employed to improve both the stability and the intestinal absorption of peptide drugs [157][158][159]. In the area of cancer drug delivery, where peptide-based chemotherapeutic agents are routinely required to be delivered to intracellular targets, increasing levels of success are being recorded with the development of innovative techniques like the use of cell-penetrating peptides, viral based-vectors, and nanoparticle-based systems [160][161][162]. It is expected that these new developments can be leveraged upon in delivering peptide-based HbS inhibitors into the intracellular compartment of RBCs.…”

Section: Benefits and Challenges Associated With Peptide-based Drugsmentioning

confidence: 99%

Rational Drug Design of Peptide-Based Therapies for Sickle Cell Disease

2019

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Sickle cell disease (SCD) is a group of inherited disorders affecting red blood cells, which is caused by a single mutation that results in substitution of the amino acid valine for glutamic acid in the sixth position of the β-globin chain of hemoglobin. These mutant hemoglobin molecules, called hemoglobin S, can polymerize upon deoxygenation, causing erythrocytes to adopt a sickled form and to suffer hemolysis and vaso-occlusion. Until recently, only two drug therapies for SCD, which do not even fully address the manifestations of SCD, were approved by the United States (US) Food and Drug Administration. A third treatment was newly approved, while a monoclonal antibody preventing vaso-occlusive crises is also now available. The complex nature of SCD manifestations provides multiple critical points where drug discovery efforts can be and have been directed. These notwithstanding, the need for new therapeutic approaches remains high and one of the recent efforts includes developments aimed at inhibiting the polymerization of hemoglobin S. This review focuses on anti-sickling approaches using peptide-based inhibitors, ranging from individual amino acid dipeptides investigated 30-40 years ago up to more promising 12-and 15-mers under consideration in recent years.Molecules 2019, 24, 4551 2 of 23 with hemoglobin reduces HbS solubility and promotes polymerization, also called sickling [3,4]. This ultimately leads to hampered O 2 binding and transport, impaired erythrocyte morphology and interaction with endothelial surfaces [5,6], premature erythrocyte rupture and anemia, painful vaso-occlusive crisis, a general poor health, and, in many cases, death [7][8][9][10][11].Despite growing understanding of the polymerization of HbS and its effects on red blood cells (RBCs), until very recently, only two drugs-hydroxyurea and L-glutamine-were approved by the United States (US) Food and Drug Administration (FDA) for the management of SCD [12]. Hydroxyurea is the most widely employed drug treatment of sickle cell anemia in different age groups [13][14][15][16][17][18]. While its clinically observed efficacy has been attributed to different effects at the cellular level [19], the most important mechanism of action relates to its ability to induce the production of fetal hemoglobin (HbF), which does not polymerize, and to increase the total concentration of hemoglobin [20,21]. Hydroxyurea remains a viable treatment option for SCD, and the concern of toxicities associated with its administration has largely been limited to side effects that resolve with medication discontinuation [22][23][24][25][26]. There have, however, been certain reports of associated malignancies [27][28][29][30][31][32], but further investigations are needed to categorically confirm these [33]. L-glutamine is the second approved drug treatment [12,34]. While its mechanism of action is not known, and only suggested to involve a reduction of oxidative stress via elevation of the levels of reduced glutathione [35,36], it is clear that it has no effect on hemo...

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“…The use of CPPs to transfect cargoes (such as small molecules, small proteins, peptides or nucleic acids) into the cell has been widely established (Li et al 2015;Singh et al 2018; Kurrikoff and Langel 2019). As vectors, CPPs can be used either in complex with the molecules of interest (e.g.…”

Section: Introductionmentioning

confidence: 99%

Mimicry of Dopamine 1 Receptor Signaling with Cell-Penetrating Peptides

Lorenzón

Gestin

Langel

2020

Int J Pept Res Ther

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Supplementary figuresSupplementary figure S1 -Cytotoxicity of Dyro 1 on SH-SY5Y cells after 2hrs treatment. SH-SY5Y cells were treated with increasing concentrations of Dyro 1 for 24hrs. The quantity of lactate dehydrogenase (LDH, a cytosolic enzyme) present in the media was measured as an indicator for membrane disruption and cell death. Data were normalized to the controls: untreated cells were used as negative control (physiological release of LDH in the cell medium; 0%), whereas cells treated with Triton X were used as the positive control (being a detergent, Triton X induces membrane disruption and complete LDH release; 100%). Control samples were examined via microscopy before LDH measurements to check for viability. The experiment was performed three times in triplicates. Due to experimental necessities, the examined Dyro 1 concentration range was 10nM -100µM, which was not enough to build a curve. However, comparing the data to the controls, it was still possible to determine the working concentration range (being its maximum, the peptide concentration inducing 20% of membrane rupture at that timepoint). The EC50 was experimentally determined to be at 100µM.Particle size (d.nm) ζ-potential (mV)

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Versatility of cell-penetrating peptides for intracellular delivery of siRNA

Cited by 55 publications

References 110 publications

Inhaled RNA Therapy: From Promise to Reality

Inhaled RNA Therapy: From Promise to Reality

Rational Drug Design of Peptide-Based Therapies for Sickle Cell Disease

Mimicry of Dopamine 1 Receptor Signaling with Cell-Penetrating Peptides

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