Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6

Dash-Wagh, Suvarna; Jacob, Stefan; Lindberg, Staffan; Fridberger, Anders; Langel, Ülo; Ulfendahl, Mats

doi:10.1038/mtna.2012.50

Cited by 17 publications

(8 citation statements)

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“…PF6 and NF70 have both been previously shown to efficiently induce RNA interference after oligonucleotide delivery in in vitro and in vivo conditions [ 14 , 16 ]. PF6 has been extensively studied and its efficacy has also been shown in primary and 3D organotypic cultures [ 41 ]. NF70, on the other hand, is a novel peptide, with most recent findings showing it can successfully deliver therapeutic miRNA into primary human keratinocytes and dendritic cells [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

et al. 2021

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Gene therapy is a powerful tool for the development of new treatment strategies for various conditions, by aiming to transport biologically active nucleic acids into diseased cells. To achieve that goal, we used highly potential delivery vectors, cell-penetrating peptides (CPPs), as oligonucleotide carriers for the development of a therapeutic approach for endometriosis and cancer. Despite marked differences, both of these conditions still exhibit similarities, like excessive, uncoordinated, and autonomous cellular proliferation and invasion, accompanied by overlapping gene expression patterns. Thus, in the current study, we investigated the therapeutic effects of CPP and siRNA nanoparticles using in vitro models of benign endometriosis and malignant glioblastoma. We demonstrated that CPPs PepFect6 and NickFect70 are highly effective in transfecting cell lines, primary cell cultures, and three-dimensional spheroids. CPP nanoparticles are capable of inducing siRNA-specific knockdown of therapeutic genes, ribonucleotide reductase subunit M2 (RRM2), and vascular endothelial growth factor (VEGF), which results in the reduction of in vitro cellular proliferation, invasion, and migration. In addition, we proved that it is possible to achieve synergistic suppression of endometriosis cellular proliferation and invasion by combining gene therapy and hormonal treatment approaches by co-administering CPP/siRNA nanoparticles together with the endometriosis-drug danazol. We suggest a novel target, RRM2, for endometriosis therapy and as a proof-of-concept, we propose a CPP-mediated gene therapy approach for endometriosis and cancer.

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Section: Discussionmentioning

confidence: 99%

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

et al. 2021

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“…They gain access to the cell interior mainly by endocytosis, and thus have the capacity to promote intracellular delivery of conjugated bioactive cargo (151). Dash-Wagh et al (80) tested the efficiency of a novel cell-penetrating peptide, PepFect6 (PF6), to deliver connexin 26 siRNA into the cochlear cells in vitro. They showed that PF6 was internalized by all cells in cochlear cultures without inducing cytotoxicity, and led to the knockdown of both connexin 26 and 30 mRNA in cochlear cells.…”

Section: Nonviral Vectorsmentioning

confidence: 99%

Toward Cochlear Therapies

Wang

Puel

2018

Physiological Reviews

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Sensorineural hearing impairment is the most common sensory disorder and a major health and socio-economic issue in industrialized countries. It is primarily due to the degeneration of mechanosensory hair cells and spiral ganglion neurons in the cochlea via complex pathophysiological mechanisms. These occur following acute and/or chronic exposure to harmful extrinsic (e.g., ototoxic drugs, noise...) and intrinsic (e.g., aging, genetic) causative factors. No clinical therapies currently exist to rescue the dying sensorineural cells or regenerate these cells once lost. Recent studies have, however, provided renewed hope, with insights into the therapeutic targets allowing the prevention and treatment of ototoxic drug- and noise-induced, age-related hearing loss as well as cochlear cell degeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes are showing promise, as are cell-replacement therapies to repair damaged cells for the future restoration of hearing in deaf people. This review begins by recapitulating our current understanding of the molecular pathways that underlie cochlear sensorineural damage, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. It then guides the reader through to the recent discoveries in pharmacological, gene and cell therapy research towards hearing protection and restoration as well as their potential clinical application.

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“…CPPs can transport to the inside of cells while carrying a wide variety of covalently or noncovalently linked cargo, including nanoparticles, peptides, proteins, antisense oligonucleotides, small-interfering RNA, double-stranded DNA, and liposomes. , Interestingly, preclinical evaluations of CPP-derived therapeutics showed promising results in various disease models, which subsequently translated into clinical trials . Therefore, CPPs represent an effective approach for delivering bioactive molecules into cells for various biomedical applications. ,− …”

Section: Introductionmentioning

confidence: 99%

Machine-Learning-Based Prediction of Cell-Penetrating Peptides and Their Uptake Efficiency with Improved Accuracy

et al. 2018

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Cell-penetrating peptides (CPPs) can enter cells as a variety of biologically active conjugates and have various biomedical applications. To offset the cost and effort of designing novel CPPs in laboratories, computational methods are necessitated to identify candidate CPPs before in vitro experimental studies. We developed a two-layer prediction framework called machine-learning-based prediction of cell-penetrating peptides (MLCPPs). The first-layer predicts whether a given peptide is a CPP or non-CPP, whereas the second-layer predicts the uptake efficiency of the predicted CPPs. To construct a two-layer prediction framework, we employed four different machine-learning methods and five different compositions including amino acid composition (AAC), dipeptide composition, amino acid index, composition-transition-distribution, and physicochemical properties (PCPs). In the first layer, hybrid features (combination of AAC and PCP) and extremely randomized tree outperformed state-of-the-art predictors in CPP prediction with an accuracy of 0.896 when tested on independent data sets, whereas in the second layer, hybrid features obtained through feature selection protocol and random forest produced an accuracy of 0.725 that is better than state-of-the-art predictors. We anticipate that our method MLCPP will become a valuable tool for predicting CPPs and their uptake efficiency and might facilitate hypothesis-driven experimental design. The MLCPP server interface along with the benchmarking and independent data sets are freely accessible at www.thegleelab.org/MLCPP .

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Intracellular Delivery of Short Interfering RNA in Rat Organ of Corti Using a Cell-penetrating Peptide PepFect6

Cited by 17 publications

References 50 publications

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

Toward Cochlear Therapies

Machine-Learning-Based Prediction of Cell-Penetrating Peptides and Their Uptake Efficiency with Improved Accuracy

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