| Peptide-mediated cellular delivery of oligonucleotide-based therapeutics in vitro: quantitative evaluation of overall efficacy employing easy to handle reporter systems. | |
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MedLine Citation:
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PMID: 19075740 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular 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 peptides (CPPs) represent an attractive concept to bypass the problem of poor membrane permeability of these charged macromolecules. While uptake per se in most cases does not represent the main obstacle of nucleic acid delivery in vitro, it becomes increasingly apparent that intracellular trafficking is the bottleneck. As a consequence, in order to optimize a given delivery system, a side-by-side analysis of nucleic acid cargo internalized and the corresponding biological effect is required to determine the overall efficacy. In this review, we will concentrate on peptide-mediated delivery of siRNAs and steric block oligonucleotides and discuss different methods for quantitative assessment of the amount of cargo taken up and how to correlate those numbers with biological effects by applying easy to handle reporter systems. To illustrate current limitations of non-viral nucleic acid delivery systems, we present own data as an example and discuss options of how to enhance trafficking of molecules entrapped in cellular compartments. |
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Authors:
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S D Laufer; T Restle |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Current pharmaceutical design Volume: 14 ISSN: 1873-4286 ISO Abbreviation: Curr. Pharm. Des. Publication Date: 2008 |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-02-12 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 9602487 Medline TA: Curr Pharm Des Country: Netherlands |
Other Details:
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Languages: eng Pagination: 3637-55 Citation Subset: IM |
Affiliation:
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Institut für Molekulare Medizin, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alternative Splicing Amino Acid Sequence Genes, Reporter* Molecular Sequence Data Oligonucleotides / administration & dosage*, therapeutic use RNA Interference RNA, Small Interfering / administration & dosage |
| Chemical | |
Reg. No./Substance:
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0/Oligonucleotides; 0/RNA, Small Interfering |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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