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Cationic PTD/CPP-mediated macromolecular delivery: charging into the cell
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA..
Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA..
2015 (English)In: Expert Opinion on Drug Delivery, ISSN 1742-5247, E-ISSN 1744-7593, Vol. 12, no 10, 1627-1636 p.Article, review/survey (Refereed) Published
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Text
Abstract [en]

Introduction: Macromolecular therapeutics, including enzymes, transcription factors, siRNAs, peptides and large synthetic molecules, can potentially be used to treat human diseases by targeting intracellular molecular pathways and modulating biological responses. However, large macromolecules have no ability to enter cells and require delivery vehicles. Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), are a diverse class of peptides that can deliver macromolecules into cells.Areas covered: In this review, we cover the uptake and usage of arginine-rich PTDs/CPPs (TAT-PTD, Penetratin/Antp and 8R). We review the endocytosis-mediated uptake of these peptides and highlight three important steps: i) cell association; ii) internalization and iii) endosomal escape. We also discuss the array of different cargos that have been delivered by cationic PTDs/CPPs as well as cellular processes and biological responses that have been modulated.Expert opinion: PTDs/CPPs have shown great potential to deliver otherwise undeliverable macromolecular therapeutics into cells for experimentation in cell culture and in animal disease models in vivo. Moreover, over 25 clinical trials have been performed predominantly using the TAT-PTD. However, more work is still needed. Endosomal escape and target-cell specificity remain two of the major future challenges.

Place, publisher, year, edition, pages
2015. Vol. 12, no 10, 1627-1636 p.
Keyword [en]
CPP, delivery, macromolecular therapeutics, PTD
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-282739DOI: 10.1517/17425247.2015.1046431ISI: 000369337400001PubMedID: 25994800OAI: oai:DiVA.org:uu-282739DiVA: diva2:919700
Funder
Swedish Research Council
Available from: 2016-04-14 Created: 2016-04-06 Last updated: 2017-11-30Bibliographically approved

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Lönn, Peter

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