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- Volume 14, Issue 34, 2008
Current Pharmaceutical Design - Volume 14, Issue 34, 2008
Volume 14, Issue 34, 2008
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Editorial [Hot Topic: Delivery, Intracellular Trafficking, and Biological Effectiveness of Oligonucleotide-Based Therapeutics Executive Editor: A. Mescalchin and G. Sczakiel]
Authors: Alessandra Mescalchin and Georg SczakielOligonucleotide-based therapeutic drugs of current interest include tools related to RNA interference (RNAi) such as short interfering RNA (siRNA), short hairping RNA (shRNA), or micro RNA (miRNA) as well as catalytic RNA and antisense oligonucleotides (asON). Based on resolved molecular patho-mechanisms of diseases and the causative involvement of genes in the development of diseases, their advantages include the m Read More
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Cellular Delivery In Vivo of siRNA-Based Therapeutics
By A. AignerRNAi interference (RNAi) is an almost standard method for the knockdown of any target gene of interest in vitro, exploring a naturally occurring catalytic mechanism. Beyond functional analyses, the downregulation of pathologically relevant genes which are aberrantly expressed in a given disease will offer novel therapeutic approaches, also with regard to otherwise ‘undruggable’ genes. RNAi is mediated by small interferin Read More
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Targeting the Lung Using siRNA and Antisense Based Oligonucleotides
Authors: Sterghios A. Moschos, Karen Spinks, Andrew E. Williams and Mark A. LindsayThe accessibility to topical administration through inhalation, combined with its large surface area, has led to speculation that the lung might offer an ideal target for the application of oligonucleotide based therapeutics. In this review, we shall critically examine the challenges facing antisense and siRNA based approaches for target validation in vivo and as potential therapeutics. In particular, we shall discuss the antisense and Read More
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Protein Transduction Revisited: Novel Insights Into the Mechanism Underlying Intracellular Delivery of Proteins
More LessClassical pharmaceutical research and development relies on the identification and validation of i) membranepermeable small molecules or ii) extracellular targets that are able to interfere with cellular key signaling pathways. During the last two decades the direct intracellular delivery of macromolecules developed into a novel paradigm to manipulate cell functions. This technique, commonly referred to as protein transdu Read More
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Peptide-Mediated Cellular Delivery of Oligonucleotide-Based Therapeutics In Vitro: Quantitative Evaluation of Overall Efficacy Employing Easy to Handle Reporter Systems
Authors: S. D. Laufer and T. RestleCellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different available non-viral systems like cationic polymers, cationic liposomes and polymeric nanoparticles, cell-penetrating Read More
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Peptide-Based Nanoparticle for Ex Vivo and In Vivo Dug Delivery
Authors: Laurence Crombez, May C. Morris, Sebastien Deshayes, Frederic Heitz and Gilles DivitaOne of the major challenges for new therapeutics molecules to enter the clinic remains improving their bioavailability and cellular uptake. Therefore, delivery has become a key stone in therapeutic development and several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs) or protein transduction domain (PTD). PTDs or CPPs were discovered t Read More
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Phosphorothioate-Stimulated Cellular Uptake of siRNA: A Cell Culture Model for Mechanistic Studies
Authors: A. Detzer, M. Overhoff, A. Mescalchin, M. Rompf and G. SczakielThe phosphorothioate(PS)-stimulated cellular uptake of naked short interfering RNA (siRNA) into mammalian cells indicates a promising new mechanistic strategy because it makes use of a caveosomal, rather than an endosomal pathway, which is used by the majority of known delivery systems. This PS-stimulated mode delivers large amounts of siRNA primarily into the perinuclear space which is related to measurable t Read More
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siRNA Modifications and Sub-Cellular Localization: A Question of Intracellular Transport?
Authors: T. Ohrt and P. SchwilleRNA interference (RNAi) is an evolutionary conserved post-transcriptional gene silencing mechanism, in which double stranded RNA effector molecules trigger the degradation of complementary mRNA transcripts. The use of RNAi to reduce gene expression with high specificity and ready availability is a powerful tool for reverse genetics and provides great therapeutic potential for targeting diseases caused by the expressi Read More
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Delivery of siRNA to the Target Cell Cytoplasm: Photochemical Internalization Facilitates Endosomal Escape and Improves Silencing Efficiency, In Vitro and In Vivo
Authors: S. Oliveira, A. Hogset, G. Storm and R.MThe prospect of introducing siRNA in a cell, to induce silencing of the corresponding gene, has encouraged research into RNAi-based therapeutics as treatment for human diseases. At present, the siRNA molecules that are in a more advanced stage of clinical evaluation have a common factor: all are delivered locally at the site of the disease. Thus, the state of the art in delivery of siRNA appears to be the local administration. Th Read More
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Volumes & issues
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Volume 31 (2025)
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Volume 30 (2024)
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Volume 29 (2023)
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Volume 28 (2022)
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Volume 27 (2021)
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Volume 26 (2020)
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Volume 25 (2019)
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Volume 24 (2018)
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Volume 23 (2017)
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Volume 22 (2016)
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Volume 21 (2015)
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Volume 20 (2014)
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Volume 19 (2013)
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Volume 18 (2012)
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Volume 17 (2011)
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Volume 16 (2010)
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Volume 15 (2009)
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Volume 14 (2008)
- Issue 36
- Issue 35
- Issue 34
- Issue 33
- Issue 32
- Issue 31
- Issue 30
- Issue 29
- Issue 28
- Issue 27
- Issue 26
- Issue 25
- Issue 24
- Issue 23
- Issue 22
- Issue 21
- Issue 20
- Issue 19
- Issue 18
- Issue 17
- Issue 16
- Issue 15
- Issue 14
- Issue 13
- Issue 12
- Issue 11
- Issue 10
- Issue 9
- Issue 8
- Issue 7
- Issue 6
- Issue 5
- Issue 4
- Issue 3
- Issue 2
- Issue 1
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Volume 13 (2007)
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Volume 12 (2006)
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Volume 11 (2005)
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Volume 10 (2004)
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Volume 9 (2003)
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Volume 8 (2002)
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Volume 7 (2001)
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Volume 6 (2000)
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